Clinical trial NCT03348514
Conditions: Advanced Solid Tumors
Sponsor: CicloMed LLC
Start date: 2018-01-15; Completion date: 2020-05-31
Enrollment: 19 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
This is a first-in-human, Phase I, multicenter, open label, dose escalation study to evaluate the DLTs and MTD and to determine the recommended Phase 2 dose (RP2D) of CPX-POM administered IV in patients with any histologically- or cytologically-confirmed solid tumor type.

Detailed description:
The study will initially employ an accelerated escalation design, with a single patient enrolled in each cohort (i.e., Single-Patient Cohorts). The initial patient will receive CPX-POM at a starting dose of 30 mg/m2. Doses will be escalated (doubling), until a ≥Grade 2 toxicity (with the exception of alopecia), is encountered. Subsequently that and all subsequent cohorts will follow a classical "3+3" dose escalation design.

Note: Fosciclopirox is the generic name for CPX-POM.

Arms: arm 1: None arm 2: None arm 3: None arm 4: None arm 5: None arm 6: None arm 7: None arm 8: None
Interventions: intervention 1: CPX-POM - 30 mg/m^2 intervention 2: CPX-POM - 60 mg/m^2 intervention 3: CPX-POM - 120 mg/m^2 intervention 4: CPX-POM - 240 mg/m^2 intervention 5: CPX-POM - 360 mg/m^2 intervention 6: CPX-POM - 600 mg/m^2 intervention 7: CPX-POM - 900 mg/m^2 intervention 8: CPX-POM - 1200 mg/m^2
Intervention descriptions: intervention 1: CPX-POM intervention 2: CPX-POM intervention 3: CPX-POM intervention 4: CPX-POM intervention 5: CPX-POM intervention 6: CPX-POM intervention 7: CPX-POM intervention 8: CPX-POM

Protocol documents:
Prot_000.pdf: 
 
CicloMed LLC 
 
CLINICAL STUDY PROTOCOL 
 
 
Study Title: 
A Phase 1, First-in-Human, Safety, Dose Tolerance, 
Pharmacokinetics, and Pharmacodynamics Study of CPX-POM 
in Patients with Advanced Solid Tumors 
 
 
Sponsor: 
CicloMed LLC  
411 Nichols Rd. 
Suite 217  
Kansas City, MO 64112 
 
 
IND No.: 
clinicaltrials.gov Identifier: 
132545 
NCT03348514 
 
 
Indication: 
Advanced Solid Tumors 
 
 
Protocol ID: 
CPX-POM-001 
 
 
 
 
Protocol Versions/Dates: 
Original Protocol Version 1.0 / 15 August 2017 
Amendment 1, Version 2.0 / 19 September 2017 
Amendment 2, Version 3.0 / 03 November 2017 
Amendment 3, Version 4.0 / 04 January 2018 
Amendment 4, Version 5.0 / 06 August 2018 
 
CONFIDENTIALITY STATEMENT 
The information contained in this document, particularly unpublished data, is the property or under control 
of CicloMed LLC, and is provided to you in confidence as an investigator, potential investigator, or 
consultant, for review by you, your staff, and an applicable Institutional Review Board or Independent 
Ethics Committee. The information is only to be used by you in connection with authorized clinical studies 
of the investigational drug described in the protocol. You will not disclose any of the information to others 
without written authorization from CicloMed LLC, except to the extent necessary to obtain informed 
consent from those persons to whom the drug may be administered. 


CicloMed LLC 
 
 
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SPONSOR SIGNATURE PAGE 
 
CicloMed LLC  
411 Nichols Rd. 
Suite 217  
Kansas City, MO 64112 
 
A Phase 1, First-in-Human, Safety, Dose Tolerance, Pharmacokinetics, and 
Pharmacodynamics Study of CPX-POM in Patients with Advanced Solid Tumors 
Amendment 4, Version 5.0, 06 August 2018. 
This protocol has been approved by CicloMed LLC.  The following signatures document this 
approval. 
 
 
 
 
 
 
William McCulloch, MB, FRCP, FFPM 
Medical Consultant 
CicloMed LLC 
 
(Date) 
 
 
 
 
 
 
 
  
Scott J Weir, PharmD, PhD 
Chief Scientific Officer [Acting] 
CicloMed LLC 
 
(Date) 
 


CicloMed LLC 
 
 
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INVESTIGATOR PROTOCOL AGREEMENT 
A Phase 1, First-in-Human, Safety, Dose Tolerance, Pharmacokinetics, and 
Pharmacodynamics Study of CPX-POM in Patients with Advanced Solid Tumors 
Amendment 4, Version 5.0, 06 August 2018 
 
By my signature, I  
• Confirm that my staff and I have carefully read and understand this protocol and the 
Investigator’s Brochure (IB) and are thoroughly familiar with the appropriate use of 
the investigational drug described herein.   
• Agree to comply with the conduct and terms of the study specified herein and with 
any other study procedures provided by the Sponsor, CicloMed LLC.   
• Agree to comply with US Food and Drug Administration (FDA) regulations, the 
International Conference on Harmonization (ICH) Good Clinical Practices (GCP) 
guidelines, the Declaration of Helsinki, and all applicable rules, regulations, and 
federal, state, and local laws relating to the conduct of clinical studies and the 
protection of human subjects.  
• Agree not to implement changes to the protocol without agreement from the Sponsor 
and prior written approval (where required) from the Institutional Review Board 
(IRB), except when necessary to eliminate an immediate hazard to the subjects.  
• Agree to onsite monitoring of the case report forms (CRFs) and source documents by 
the Sponsor or designee and to audit by the Sponsor or designee and appropriate 
regulatory authorities, including, but not limited to, the FDA and IRB inspectors. 
• Agree to supervise the conduct of the study and maintain responsibility for training 
and supervising all personnel who have been delegated responsibilities under my 
leadership.  The protocol and other important study materials will be available to 
study staff throughout the conduct of the study. 
 
 
 
Investigator's Signature 
 
Date 
 
 
 
Print Name 
 
 
 


CicloMed LLC 
 
 
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TABLE OF CONTENTS 
 
1. 
PROTOCOL SUMMARY ........................................................................................................................ 7 
1.1. 
Synopsis ....................................................................................................................................... 7 
1.2. 
Study Diagram ............................................................................................................................ 11 
1.3. 
Schedule of Assessments ............................................................................................................ 13 
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS .......................................................... 18 
2. 
INTRODUCTION................................................................................................................................... 21 
3. 
OBJECTIVES ......................................................................................................................................... 23 
4. 
STUDY DESIGN .................................................................................................................................... 24 
4.1. 
Overall Design ............................................................................................................................ 24 
4.2. 
Planned Doses for Dose Escalation ............................................................................................. 26 
4.3. 
Rationale for Study Design ......................................................................................................... 27 
4.4. 
Dose Selection ............................................................................................................................ 28 
4.5. 
End of Study Definition .............................................................................................................. 28 
5. 
STUDY POPULATION .......................................................................................................................... 29 
5.1. 
Inclusion Criteria ........................................................................................................................ 29 
5.2. 
Exclusion Criteria ....................................................................................................................... 30 
5.3. 
Meals and Dietary Considerations ............................................................................................... 32 
5.4. 
Screen Failures ........................................................................................................................... 32 
6. 
TREATMENTS ...................................................................................................................................... 33 
6.1. 
Investigational Product ............................................................................................................... 33 
6.1.1. 
Description of Investigational Product ....................................................................... 33 
6.1.2. 
Packaging and Labeling ............................................................................................. 33 
6.1.3. 
Storage and Handling ................................................................................................ 33 
6.1.4. 
Dosage and Administration........................................................................................ 33 
6.1.5. 
Dose Modifications ................................................................................................... 34 
6.1.6. 
Compliance ............................................................................................................... 34 
6.1.7. 
Accountability ........................................................................................................... 34 
6.2. 
Prior and Concomitant Medications ............................................................................................ 35 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PATIENT 
DISCONTINUATION/WITHDRAWAL ................................................................................................ 36 
7.1. 
Discontinuation of Study Treatment ............................................................................................ 36 
7.2. 
Patient Discontinuation/Withdrawal from the Study .................................................................... 36 
7.3. 
Lost to Follow Up ....................................................................................................................... 36 
8. 
STUDY ASSESSMENTS ....................................................................................................................... 38 
8.1. 
Cancer Evaluation ....................................................................................................................... 38 
8.2. 
Safety Assessments ..................................................................................................................... 38 
8.2.1. 
Adverse Events and Serious Adverse Events ............................................................. 38 
8.2.2. 
Pregnancy .................................................................................................................. 43 
8.2.3. 
Other Safety and Screening Assessments ................................................................... 44 
8.3. 
Pharmacokinetic Assessments ..................................................................................................... 48 
8.4. 
Pharmacodynamic Assessments .................................................................................................. 48 
9. 
STATISTICAL CONSIDERATIONS ..................................................................................................... 49 
9.1. 
Number of Patients ..................................................................................................................... 49 
9.2. 
Analysis Sets .............................................................................................................................. 49 
9.2.1. 
Safety ........................................................................................................................ 49 
9.2.2. 
Pharmacokinetics....................................................................................................... 49 
9.3. 
Data Handling Conventions ........................................................................................................ 49 
9.4. 
Demographic Data and Baseline Characteristics ......................................................................... 49 
9.5. 
Safety Analysis ........................................................................................................................... 49 
9.5.1. 
Determination of Maximum Tolerated Dose .............................................................. 50 
9.5.2. 
Extent of Exposure .................................................................................................... 50 
9.5.3. 
Adverse Events .......................................................................................................... 50 


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9.5.4. 
Laboratory Evaluations .............................................................................................. 50 
9.5.5. 
Other Safety Evaluations ........................................................................................... 51 
9.6. 
Pharmacokinetic Analysis ........................................................................................................... 51 
9.6.1. 
Pharmacokinetics in Plasma ...................................................................................... 51 
9.6.2. 
Pharmacokinetics in Urine ......................................................................................... 52 
9.6.3. 
Covariates and Pharmacokinetics ............................................................................... 52 
9.7. 
Pharmacodynamic Analyses ....................................................................................................... 52 
9.8. 
Interim Analyses ......................................................................................................................... 53 
10. REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS .................................. 54 
10.1. 
Regulatory and Ethical Considerations ........................................................................................ 54 
10.1.1. 
Institutional Review Board/Ethics Committee ........................................................... 54 
10.1.2. 
Ethical Conduct of the Study ..................................................................................... 54 
10.1.3. 
Informed Consent ...................................................................................................... 55 
10.1.4. 
Confidentiality........................................................................................................... 55 
10.2. 
Study Oversight .......................................................................................................................... 56 
10.2.1. 
Data Quality Assurance ............................................................................................. 56 
10.2.2. 
Source Documents ..................................................................................................... 56 
10.2.3. 
Study and Site Closure .............................................................................................. 56 
10.2.4. 
Reporting of Results and Publications........................................................................ 57 
10.2.5. 
Study Files and Retention of Records ........................................................................ 58 
10.2.6. 
Case Report Forms .................................................................................................... 59 
10.2.7. 
Inspections ................................................................................................................ 59 
10.2.8. 
Protocol Compliance ................................................................................................. 59 
10.2.9. 
Study Discontinuation ............................................................................................... 59 
11. REFERENCES ....................................................................................................................................... 60 
12. APPENDIX ............................................................................................................................................. 62 
 
 


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LIST OF IN-TEXT TABLES 
 
Table 1. 
Schedule of Assessments ........................................................................................... 14 
Table 2. 
Dose Escalation Procedures ....................................................................................... 25 
Table 3. 
Example Doses for Accelerated Titration Cohorts ...................................................... 27 
Table 4. 
Example Doses for Standard Dose Escalation Cohorts ............................................... 27 
Table 5. 
Eastern Cooperative Performance Status .................................................................... 45 
Table 6. 
Listing of Required Screening and Safety Laboratory Parameters .............................. 47 
 
 
LIST OF IN-TEXT FIGURES 
 
Figure 1. 
Study Design ............................................................................................................. 12 
 
 
LIST OF APPENDICES 
Appendix 1. 
RECIST Criteria Guidance ........................................................................................ 62 
 


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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
CicloMed LLC 
411 Nichols Rd. 
Suite 217  
Kansas City, MO 64112 
 
Study Title:  
A Phase 1, First-in-Human, Safety, Dose Tolerance, Pharmacokinetics, and 
Pharmacodynamics Study of CPX-POM in Patients with Advanced Solid 
Tumors 
IND Number: 
132545 
Study Centers 
Planned: 
Approximately 6 centers in the United States 
Objectives: 
The primary objective of this study is as follows: 
• 
To evaluate the dose limiting toxicities (DLTs) and maximum tolerated 
dose (MTD) of ciclopirox phosphoryloxymethyl ester (CPX-POM) 
administered intravenously (IV) and establish the CPX-POM dose 
recommended for further investigation. 
The secondary objectives of this study are as follows:  
• 
To characterize the plasma and urine pharmacokinetics (PK) of CPX-POM 
and its metabolites following single and multiple dose administration;  
• 
To identify preliminary anti-tumor activity of CPX-POM;  
• 
To determine urine β-glucuronidase activity in patients participating in the 
trial. 
The exploratory objectives of this study are as follows: 
• 
To characterize the pharmacologic effects of CPX-POM on circulating 
biomarkers of Wnt and Notch cell signaling pathways; 
• 
To explore pharmacodynamic (PD) relationships between changes in 
circulating biomarkers and drug and/or metabolites exposure and other 
outcomes. 
Study Design: 
This is a first-in-human, Phase 1, multicenter, open label, dose escalation study 
to evaluate the DLTs and MTD and to determine the recommended Phase 2 
dose (RP2D) of CPX-POM administered IV in patients with any histologically- 
or cytologically-confirmed solid tumor type.  Secondary objectives include 
characterization of the safety and PK profile of CPX-POM and identification of 
preliminary anti-tumor activity in this patient population.  Biomarkers and their 
relationship to PK and other outcomes will be examined as an exploratory 
objective. 
The study will initially employ an accelerated escalation design, with a single 
patient enrolled in each cohort (i.e., Single-Patient Cohorts).  The initial patient 
cohort will receive CPX-POM at a starting dose of 30 mg/m2.  Doses will be 
escalated in 100% increments (i.e., doubling), until a ≥Grade 2 toxicity (with 
the exception of alopecia), as determined according to the United States (US) 


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National Cancer Institute (NCI) Common Terminology Criteria for Adverse 
Events (CTCAE), version 4.03, is encountered, at which point that cohort and 
all subsequent cohorts will follow a classical “3 + 3” dose escalation design 
(i.e., Standard Dose Escalation Cohorts).   
After each cohort is completed, a Safety Review Committee (SRC) comprised 
of the CRO Medical Monitor, Principal Investigator(s), and Sponsor 
representatives will meet to discuss the data and decide upon the next dose 
escalation.  Doses in the standard cohorts will be escalated in 25 to 50% 
increments, based on SRC decision, until the MTD is reached.  In addition, 
after completion of Cycle 1 for the first 4 to 6 patients, the SRC will review 
safety, PK, and PD data to determine if any changes to the dosing schedule are 
indicated.  
Intrapatient dose escalation will not be allowed in any patient at any time. 
Each patient in a dose cohort must have received at least 80% of their 
CPX-POM doses, unless due to toxicity, during Cycle 1 with follow-up safety 
evaluations through Day 22 (or Cycle 2, Day 1, if continuing in the study) to be 
eligible for the assessment of DLT.   
Patients may continue to receive cycles of CPX-POM until progression of 
disease, intolerable toxicity occurs, or another withdrawal criterion applies. 
Approximately 24 patients will be enrolled in the Single-Patient and Standard 
Dose Escalation Cohorts to establish the MTD.  In addition to these estimated 
24 patients, Expansion Cohort(s) may be enrolled after the MTD is reached to 
either explore different dosing schedules, increase the experience with a 
particular tumor type (e.g., muscle invasive bladder cancer [MIBC]), or to 
examine the safety and anti-tumor activity of CPX-POM in combination with 
certain other anticancer agents.   
Dose escalation procedures will be conducted as follows:    
 
Accelerated Titration (Single-Patient Cohorts; n=1 each) 
 
No ≥Grade 2 adverse 
events (AEs) 
• Continue evaluation of single-patient dose 
cohorts. 
• Escalate by 100% to next dose level. 
 
At least 1 ≥Grade 2 
AE not meeting the 
definition of DLT 
• Expand current and subsequent cohorts to at least 
3 patients (see Standard Dose Escalation Scheme 
below). 
 
1 DLT  
• Expand current cohort up to 6 patients or until 
2 DLTs are encountered (Standard Dose 
Escalation Scheme below). 
 
Standard Dose Escalation (Standard Cohorts; n=3 to 6 each) 
 
No DLT 
• Escalate by 25−50% to next dose level. 
 
1 DLT in ≤3 patients 
• Expand cohort up to 6 patients. 
 
1 DLT in 6 patients 
• Escalate by 25−50% to next dose level. 
 
> 1 DLT in ≤6 
patients 
• MTD reached; stop dose escalation.   
• Possibly explore intermediate doses for the RP2D. 


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A Dose-Limiting Toxicity will be defined as any of the following if deemed 
related to study drug: 
• 
Grade 4 thrombocytopenia of any duration  
• 
Grade 3 thrombocytopenia with significant hemorrhage of any duration  
• 
Grade 4 absolute neutrophil count (ANC) >5 days  
• 
Febrile neutropenia  
• 
Grade ≥3 non-hematologic toxicity of any duration, except:  
o Grade 3 nausea, vomiting, or diarrhea and Grade 4 vomiting or diarrhea 
in the absence of maximal medical therapy that resolves in 72 hours  
o Grade 3 fatigue lasting <5 days 
o Grade 3 hypertension that can be controlled with medical therapy 
o An increase of indirect (unconjugated) bilirubin indicative of 
M. Meulengracht/Gilbert’s syndrome 
o Serum lipase and/or serum amylase CTCAE Grade 3 ≤7 consecutive 
days without clinical signs or symptoms of pancreatitis  
• 
Delay in study drug due to toxicity for >2 weeks   
• 
Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) 
>3xULN with bilirubin >2x the upper limit of normal (ULN) without 
another explanation (e.g., cholestasis)  
Any patient who is unable to receive 80% of the expected dose of CPX-POM 
(i.e., patients who are unable to receive at least 4 of the 5 scheduled doses) 
because of AEs will be considered to have a DLT. 
Number of 
Patients 
Planned: 
Approximately 24 patients will be enrolled in dose escalation cohorts to 
establish the MTD.  In addition to these estimated 24 patients, Expansion 
Cohort(s) may also be enrolled after the MTD is reached.  
Target 
Population: 
Patients with any histologically- or cytologically-confirmed solid tumor type 
that is refractory to standard therapy.   Patients should only be included if no 
therapy exists or if they have received all standard therapies that would be 
potentially curative or might provide significant benefit.   
Duration of 
Study: 
Patients who receive one treatment cycle will be in this study for up to 
approximately 8 weeks:  up to a 28-day Screening period, a 21-day Treatment 
cycle, and a Follow-up period out to 28 ± 5-days after the last dose (i.e., 
approximately Day 33).  After the first treatment cycle, patients may continue 
to receive cycles of CPX-POM until progression of disease, intolerable toxicity 
occurs, or another withdrawal criterion applies.   


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Diagnosis and 
Main Eligibility 
Criteria: 
Patients eligible for enrollment in this study will be adults with any 
histologically- or cytologically-confirmed metastatic or advanced-stage solid 
tumor that is refractory to standard therapy.  Patients should only be included if 
no therapy exists or if they have received all standard therapies that would be 
potentially curative or might provide significant benefit.  Patients must have a 
life expectancy ≥3 months, an Eastern Cooperative Oncology Group (ECOG) 
Performance Status 0 or 1, no significant ischemic heart disease, adequate 
hepatic function, and a baseline glomerular filtration rate (GFR) 
>50 mL/min/1.73m2.  Females must not be pregnant and, if of childbearing 
potential, must use an effective method of contraception to avoid pregnancy 
during and for 3 months after participation in the trial.  
Patients who have any risk factor for torsade de pointes or any uncontrolled or 
severe intercurrent medical condition, or who have had major surgery or prior 
systemic chemotherapy or radiation therapy within the previous 4 weeks are 
excluded. 
Test Product, 
Dose, and Mode 
of 
Administration: 
Escalating doses of CPX-POM will be administered by 10-minute IV infusion 
once daily on Days 1-5 of each 21-day cycle.   
After completion of Cycle 1 for the first 4 to 6 patients, the SRC will review 
safety, PK, and PD data to determine if any changes to the dosing schedule are 
indicated (e.g., adding an additional 5 days of dosing to each treatment cycle).   
Patients may continue to receive cycles of CPX-POM until progression of 
disease, intolerable toxicity occurs, or another withdrawal criterion applies.  
The starting dose will be 30 mg/m2.   
Reference 
Therapy, Dose, 
and Mode of 
Administration: 
Not applicable. 
Criteria for 
Evaluation: 
Safety: 
Safety and tolerability will be based on an assessment of AEs, physical 
examinations, vital signs, electrocardiograms (ECGs), clinical laboratory tests, 
ophthalmologic assessments, and concomitant medications.   
The MTD will be defined as the dose BELOW that dose which causes DLTs in 
≥33% of patients. 
Pharmacokinetics: 
Serial blood (plasma) samples and complete urine will be collected over 
24-hour periods starting after the first (Day 1) and fifth (Day 5) doses of 
CPX-POM during Cycle 1 to characterize single dose and steady-state plasma 
and urine PK of CPX-POM, ciclopirox (CPX), and ciclopirox glucuronide 
(CPX-G).  If patients are unable or unwilling to attend the required 12 hours of 
clinic visitation required for steady-state PK sampling on Day 5 of Cycle 1, the 
steady-state PK sampling may be postponed to Day 5 of Cycle 2.  Urine β-
glucuronidase activity will be measured prior to and after 5 days of CPX-POM 
administration (i.e., on Days 1 and 5 of Cycle 1).   
Pharmacodynamics: 
Blood will be collected to characterize the effects of CPX-POM on circulating 
biomarkers of Wnt and Notch cell signaling pathways.  Plasma and peripheral 
blood mononuclear cells (PBMCs) will be isolated from blood.  Vascular 


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endothelial growth factor (VEGF), interleukin (IL)-6, and IL-8 concentrations 
will be measured in plasma by enzyme-linked immunoassay (ELISA).  
Quantitative real-time polymerase chain reaction (qRT-PCR) will be used to 
characterize gene expression of circulating biomarkers of Wnt and Notch 
signaling pathways in PBMCs. 
Statistical 
Methods: 
Safety: 
Safety data will be presented in by-patient listings.  Categorical safety 
endpoints will be summarized by frequency of events/abnormalities for each 
dose group and overall.  Continuous safety endpoints will be summarized using 
descriptive statistics (number of subjects [n], mean, standard deviation, median, 
first quartile [Q1], third quartile [Q3], minimum, maximum) for each dose 
group and overall.   
Pharmacokinetics: 
Standard PK parameters will be derived from resultant plasma and urine drug 
and metabolite concentration-time data using non-parametric methods.  PK 
parameters will be summarized using descriptive statistics.   
Pharmacodynamics: 
A logistic regression will be used to estimate the predicted toxicity probability 
at each dose level.  Relationships between dose, drug and metabolite exposure, 
PD response, and other endpoints (i.e., ECGs, toxicity, safety, and biomarker 
endpoints) may be explored using descriptive statistics, and/or additional 
PK/PD modeling. 
 
This study will be conducted in accordance with the guidelines of current GCPs including 
archiving of essential documents.  
1.2. 
Study Diagram 
The study design is illustrated in Figure 1. 
 


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Figure 1. 
Study Design 
 
Abbreviations:  CPX-POM = ciclopirox phosphoryloxymethyl ester; D = day; PD = pharmacodynamic; PK = pharmacokinetic; V = visit. 
 
Study Day:
D -14 to -1
Informed consent and screening eligibility assessments 
28 ± 5 days 
after end of 
last cycle 
CPX-POM dosing, PK (pre-dose [trough] sample , Cycle 1 only), and 
safety assessments,
Safety follow-up visit
V1
Study Visit:
D1
V2
CPX-POM dosing, PK (Cycle 1 only) , PD, and safety assessments
D2
V3
D 3-D4
V4–V5
D22/
early 
termination
If  final  treatment cycle, patient returns for Safety and PD 
assessments on  Day 22.  If additional cycles are planned, 
patient skips this visit and restarts schedule at Day 1 (except for PK).  
D10
Cycle 1 only
CPX-POM dosing and safety assessments
No dosing  or study visits, Days 7-9
D5
V6
CPX-POM dosing, PK (Cycle 1 only) , PD, and safety assessments
D 6
V7
Trough PK sample, (Cycle 1 only)  and safety assessments
D 7–D9
D 11–D21
V8
No dosing  or study visits, Days  11-21
Safety assessments (Cycle 1 only)


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1.3. 
Schedule of Assessments 
The schedule of assessments is shown in Table 1. 
 


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Table 1. 
Schedule of Assessments 
Study Procedure 
Screening 
Period 
Treatment Period 
Follow-up 
Period 5 
Study Days: 
D -28 to  
D -1 
D1 1 
D2 
D3 
D4 
D5 1 
D6 
D10 2 
(Cycle 1 
only) 
D22  
(last cycle) 4 
28 (±5) days 
post last dose 
or at early 
termination 
Study Visits: 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
ECOG Performance Status 
X 
 
 
 
 
 
 
 
 
X 
Medical history 
X 
 
 
 
 
 
 
 
 
 
HIV and hepatitis screening 6 
X 
 
 
 
 
 
 
 
 
 
Pregnancy test 7 
X 
X 
 
 
 
 
 
 
 
 
Cancer evaluation 8 
X 
X 
 
 
 
 
 
 
 
 
CT or MRI 
X 
 
 
 
 
 
 
 
 
 
MUGA or ECHO 
X 
 
 
 
 
 
 
 
 
 
Hematology 9 
X 
X 
 
 
X 
 
 
X 
X 
X 
Clinical chemistry 10 
X 
X 
 
 
X 
 
 
X 
X 
X 
Thyroid panel 11 
X 
X 
 
 
 
 
 
 
 
 
Coagulation test 12 
X 
X 
 
 
 
 
 
 
 
 
Urinalysis 13 
X 
X 
 
 
 
X 
 
X 
X 
X 
Full physical exam 14 
X 
 
 
 
 
 
 
 
 
X 
Assess for physical 
symptoms/toxicities 15 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Ophthalmologic exam 15 
X 
 
 
 
 
 
 
 
 
X 
Vital signs 16 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECG 17 
X 
X 
 
 
 
X 
 
 
 
X 
Start 24- hour Holter monitor 18 
 
X 
 
 
 
 
 
 
 
 


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Study Procedure 
Screening 
Period 
Treatment Period 
Follow-up 
Period 5 
Study Days: 
D -28 to  
D -1 
D1 1 
D2 
D3 
D4 
D5 1 
D6 
D10 2 
(Cycle 1 
only) 
D22  
(last cycle) 4 
28 (±5) days 
post last dose 
or at early 
termination 
Study Visits: 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PK blood samples 19 
 
X 
X 
 
 
X 
X 
 
 
 
PK urine samples 20 
 
X 
X 
 
 
X 
X 
 
 
 
β glucuronidase urine sample 21 
 
X 
 
 
 
X 
 
 
 
 
Biomarker blood sample 22 
 
X 
 
 
 
X 
 
 
X 
X 
Body surface area 23 
 
X 
 
 
 
 
 
 
 
 
CPX-POM infusions 24 
 
X 
X 
X 
X 
X 
 
 
 
 
Abbreviations:  ALP = alkaline phosphatase; ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time; AST = aspartate 
aminotransferase; BSA = body surface area; BUN = blood urea nitrogen; CPX-=POM = ciclopirox phosphoryloxymethyl ester; CT = computed tomography; 
D = day; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EDTA = ethylenediamine tetraacetic acid; eGFR = estimated 
glomerular filtration rate; GGT = gamma glutamyl transferase; HIV = human immunodeficiency virus; IV = intravenous; MUGA = multi-gated acquisition; 
MRI = magnetic resonance imaging; PBMC = peripheral blood mononuclear cell; PD = pharmacodynamic; PK = pharmacokinetic; PT = prothrombin time; 
RBC = red blood cell; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid stimulating hormone; V = visit; WBC = white blood cell.   
1. On Days 1 and 5 of Cycle 1, patients will be required to stay at the clinical research unit for at least 12 hours for PK sampling and other 
assessments.  If patients are unable or unwilling to attend the required 12 hours of clinic visitation required for steady-state PK sampling on Day 5 
of Cycle 1, the steady-state PK sampling may be postponed to Day 5 of Cycle 2.  To shorten the duration of the Cycle 1, Day 1 visit, if needed, the 
safety laboratory blood samples required for this visit may be drawn up to 3 days before Day 1.  
2. The Day 10 (Visit 8) study visit will only be required during Cycle 1.   
3. After cycle 1; visit windows can be considered on a case by case basis due to events such as holidays; Cycle 1 needs to occur without visit 
windows. D6 can occur +2 calendar days for cycles after Cycle 1 is completed. 
4. If final treatment cycle, patient returns for assessments on Day 22.  If additional cycles are planned, patient skips this visit and restarts schedule at 
Day 1 (except for PK).  Patients may continue to receive cycles of CPX-POM until progression of disease, intolerable toxicity occurs, or another 
withdrawal criterion applies. 


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5. The Follow-up visit will occur 28±5 days after the last dose of CPX-POM administered during the last treatment cycle.  Or, in the event that a 
patient discontinues from the study prematurely, the site will make every effort to perform the assessments listed for this study visit.  
6. Hepatitis screening will include tests for Hepatitis A, Hepatitis B, and Hepatitis C.  
7. Pregnancy tests will be required only for women of child bearing potential at Screening and before dosing on Day 1 of each treatment cycle.  Urine 
or serum pregnancy tests are acceptable.  
8. Cancer evaluation will include determination of staging and metastases for screening purposes (see Section 8.1).  Disease response assessments will 
be performed for patients with measurable disease within 28 days prior to the first dose of CPX-POM and repeated at the end of every second cycle 
(i.e., at approximately 6-week intervals).  During the Dose-Escalation Phase of the study, Screening cancer evaluations may be performed up to 28 
days before Cycle 1, Day 1.  For patients enrolled in any Expansion cohorts, Screening cancer evaluations must be performed within 28 days of 
Cycle 1, Day 1.    
9. Hematology will include measurement of hemoglobin, hematocrit, platelets, RBC, reticulocytes, and WBC with differential.  To shorten the 
duration of the Cycle 1, Day 1 visit, if needed, the safety laboratory blood samples required for this visit may be drawn up to 3 days before Day 1 
(Cycle 1 only).   
10. Clinical chemistry will include measurement of potassium, sodium, chloride, glucose, BUN, creatinine, creatinine clearance, ALT, AST, ALP, 
GGT, alkaline phosphatase, indirect bilirubin, direct bilirubin, total bilirubin, total protein, albumin, calcium, bicarbonate, magnesium, phosphate, 
lipase, and amylase.  To shorten the duration of the Cycle 1, Day 1 visit, if needed, the safety laboratory blood samples required for this visit may 
be drawn up to 3 days before Day 1. 
11. Thyroid panel will include TSH, free T4, and free and total T3 and will be repeated on D1 of each cycle.  
12. Coagulation tests will include PT and aPTT and will be repeated on D1 of each cycle.  
13. Urinalysis will include color, turbidity, pH, specific gravity, glucose, ketones, nitrites, bilirubin, urobilirubin, protein, RBCs, WBCs, epithelial cells, 
casts, crystals, and bacteria, and eGFR at Screening only. 
14. A full physical examination will be conducted at Screening and at Follow-up.  At each other study visit, patients will be assessed for continued 
dosing and any possible physical symptoms/toxicities and a physical examination may be performed, if indicated.  Body weight should be measured 
at each study visit.  Height should be measured at Screening.  
15. Ophthalmology evaluations will be conducted at least on Day 1 and at Follow-up by a qualified ophthalmologist and will include visual acuity, 
pupil exam, confrontation visual field, extraocular motility and alignment, interior slit lamp examination, and dilated fundus examination of the 
retina.  Additional ophthalmology evaluations may be performed at any other time, if indicated, as determined by the investigator.  
16. Vital signs will be measured before any blood draws scheduled for the same time point.  Vital signs will include blood pressure, respiratory rate, 
pulse, oxygen saturation, and temperature.  On Days 1 and 5, vital signs will be measured at pre-dose and at 6-hour intervals post-dose.  
17. At Screening, 12-lead ECGs will be performed in triplicate, with each measurement separated by 2 minutes.  The average of the 3 screening ECGs 
will be used to calculate QTc interval to determine study eligibility.  Thereafter, single 12-lead ECGs will be performed for all patients prior to drug 
administration on Days 1 and 5 of Cycle 1; on Day 1 of each subsequent treatment cycle; and at the Final Study visit.   
18. Cycle 1:  Starting on Day 1 of Cycle 1, digital Holter monitoring will be performed from 45 minutes pre-dose through 24 hours post-dose.  ECG 
extractions of the continuous Holter recordings will be performed at 45, 30, and 15 minutes pre-dose and at specific post-dose time points 


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coinciding with the serial blood sampling time points for pharmacokinetics.  Patients will be instructed to assume a supine position 5-10 minutes 
prior to each serial blood sampling time point and remain supine throughout the 5-minute ECG extraction period just prior to serial blood sample 
collection.  During the 24-hour Holter monitoring period, a 12-lead ECG tracing may be printed out at any time while the patient is in the clinic at 
the discretion of the investigator.  If for any reason Holter monitoring is not performed in conjunction with the PK sampling on Day 1 or the 
tracings are of poor quality, Holter monitoring may be performed in conjunction with the PK sampling on Day 5. 
19. Cycle 1:  Serial, 3-mL blood samples will be taken for determination of plasma CPX-POM and metabolites concentrations during Cycle 1 at 0.25, 
0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0, and 24.0 hours following completion of the 10-minute IV infusion on Day 1 and on Day 5.  Each 
PK sample should be collected as close as possible to the planned time. The 12.0 hour collection can have a +/- 1-hour window (collect within 11 to 
13 hours) and the exact time must be recorded.  The actual date and time of each blood sample collection will be accurately recorded. 
20. Cycle 1:  Complete 24-hour urine samples for determination of CPX-POM and metabolites concentrations, and measurement of urine volume will 
be obtained from each patient in urine collection and storage containers during Cycle 1.  A sample will be taken at pre-dose on Day 1, and complete 
urine samples will be collected at 0-12 and 12-24 hour collection intervals post-dose on Days 1 and 5.  The 12 hour collection can have a +/- 1-hour 
window (collect within 11 to 13 hours) and the exact time must be recorded. 
21. Cycle 1:  Urine β-glucuronidase activity will be determined in the complete 24-hour urine samples collected on Day 1 and Day 5 of Cycle 1.  
22. 7-mL blood samples will be obtained in EDTA-containing blood collection tubes at pre-dose on Day 1 and Day 5 of each treatment cycle, and on 
Day 22 of the last treatment cycle.  Plasma and buffy coat (PBMCs) will be isolated, transferred to storage tubes, and stored frozen. 
23. BSA will be calculated by the site personnel using the Dubois method of calculation using screening height and baseline weight measurements.  
BSA is to be recalculated before study drug administration on Day 1 of every other treatment cycle, starting with Cycle 3 and the patient’s study 
drug dose adjusted accordingly. 
24. CPX-POM infusions will be administered once every 24 hours as 10-minute IV infusions on Days 1-5 of each 21-day treatment cycle.  After 
completion of Cycle 1 for the first 4 to 6 patients, the SRC will review safety, PK, and PD data to determine if any changes to the dosing schedule 
are indicated (e.g., adding an additional 5 days of dosing to each treatment cycle). 
 


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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS 
AE 
adverse event 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
aPTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve following a single dose on Day 1 
AUCss 
area under the concentration-time curve over the dosing interval at steady-
state following drug administration on Day 14 
AUC[0-t] 
area under the concentration-time curve following administration of a 
single dose on Day 1 
AUC[t-∞] 
area under the concentration-time curve following administration of a 
single dose on Day 1 from the last quantifiable concentration (t) to infinity 
AUCinf  
area under the curve from time zero to extrapolated infinite time [AUC(0 
∞)] following administration of a single dose on Day 1 as the sum of 
AUC[0-t] + AUC(t-∞) 
BSA 
body surface area 
CLr 
single dose (Day 1) and steady-state (Day 14) renal clearance 
CLs 
systemic clearance following administration of a single dose on Day 1 
CLss 
systemic clearance at steady-state 
Cmax 
the maximum observed serum/plasma/PBMC concentration of drug 
Cssmax 
the maximum observed plasma concentration of drug and metabolites 
observed at steady-state over the dosing interval 
CPX 
ciclopirox 
CPX-G 
ciclopirox glucuronide 
CPX-O 
ciclopirox olamine 
CPX-POM 
ciclopirox phosphoryloxymethyl ester (ciclopirox prodrug) 
CRF 
case report form(s) 
CRO 
contract research organization  
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLT 
dose limiting toxicity 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
ELISA 
enzyme-linked immunoassay 


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FDA 
(United States) Food and Drug Administration 
GCP 
Good Clinical Practice 
GFR 
glomerular filtration rate 
GGT 
gamma glutamyl transferase 
GLP 
Good Laboratory Practices 
HNSTD 
highest non-serious toxic dose 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council on Harmonisation 
IL 
Interleukin 
IRB 
institutional review board 
IV 
intravenous 
LC-MS/MS 
liquid chromatography tandem mass spectroscopy 
MedDRA 
Medical Dictionary for Regulatory Activities 
MIBC 
muscle invasive bladder cancer 
mRNA 
messenger RNA 
MTD 
maximum tolerated dose 
MUGA 
multi-gated acquisition 
n 
number of subjects 
NCI 
National Cancer Institute 
NOAEL 
no observed adverse effect level 
PBMC 
peripheral blood mononuclear cell 
PD 
pharmacodynamic 
PK 
pharmacokinetic 
PT 
prothrombin time 
Q1 
first quartile 
Q3 
third quartile 
qRT-PCR 
quantitative real-time polymerase chain reaction 
QTc 
corrected QT interval 
QTcF 
QT interval corrected using Fridericia’s formula 
RECIST 
Response Evaluation Criteria for Solid Tumors 
RNA 
ribonucleic acid 
RP2D 
recommended phase 2 dose 
SAE 
serious adverse event 
SOC 
system organ class 


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SRC 
Safety Review Committee 
SUSAR 
suspected unexpected serious adverse reaction 
tmax 
the time (observed time point) of Cmax 
tssmax 
the time (observed time point) of Cmaxss 
t½ 
apparent elimination half-life 
ULN 
upper limit of the normal range 
US 
United States 
Vd 
apparent volume of distribution  
VEGF 
vascular endothelial growth factor 
Vss 
Steady-state volume of distribution  
λ 
apparent first-order elimination rate constant 


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2. 
INTRODUCTION 
CPX-POM is a prodrug of ciclopirox (CPX).  CPX is a synthetic antifungal agent approved 
for topical dermatologic use in the treatment of a broad spectrum of fungal organisms 
(Gupta, 2001).  CPX and ciclopirox olamine (CPX-O) are contained in a number of marketed 
topical drug products.  CPX also exerts antibacterial activity against many Gram-positive and 
Gram-negative bacteria (Abrams et al, 1991).  CPX is a hydroxypyridone that is structurally 
unrelated to other antifungal agents and has a unique and complex mode of action.  CPX is 
thought to act through the chelation of polyvalent metal cations, such as iron and aluminum, 
resulting in the inhibition of the metal-dependent enzyme systems (e.g., cytochromes, 
catalase, peroxidase), thus disrupting cellular activities, such as inhibiting degradation of 
peroxides within the fungal cells (Gupta and Plott, 2004) and mitochondrial electron 
transport processes and energy production (Sakurai et al, 1978; Gupta et al, 1994).  It is also 
thought that CPX affects the cytoplasmic membranes, inhibiting transport of essential 
elements in the fungal cell, disrupting the synthesis of DNA, ribonucleic acid (RNA), and 
protein (Gupta and Plott, 2004).  In addition, CPX may have anti-inflammatory activity as 
demonstrated by its ability to inhibit the synthesis of prostaglandins and leukotrienes in 
human polymorphonuclear cells (Abrams et al, 1991) and to inhibit the formation of 5-
lipoxygenase and ciclo-oxygenase (Bohn and Kraemer, 2000; Hanel et al, 1991).   
CPX has demonstrated in vivo and/or in vitro anticancer activity in at least 17 types of solid 
tumor and hematologic cancers (CPX-POM Investigators Brochure, 2017).  CPX modulates 
iron-dependent enzymes and signaling pathways resulting in inhibition of cell growth, 
proliferation, and survival.  CPX has been demonstrated to chelate intracellular iron in 
human cancer cells (Kwong et al, 2015; Eberhard et al, 2009; Sidarovich et al, 2015), which 
plays an important role in cancer cell death resulting from exposure to CPX (Clement et al, 
2002; Szüts and Krude, 2004; Eberhard et al, 2009; Sidarovich et al, 2015).  CPX exposure 
altered expression of 54 proteins in stem cells, including those associated with nucleotide 
binding, biosynthetic processes, gene expression, regulation of transcription, cell cycle 
processes, RNA and messenger RNA (mRNA) processing, and embryonic development 
(Dihazi et al, 2011). 
Scientists at the University of Kansas synthesized the phosphoryloxymethyl ester of CPX, 
CPX-POM to enable parenteral administration of CPX.  In contrast to CPX and CPX-O, 
CPX-POM has high water solubility and is readily formulated for parenteral administration.   
Pharmacokinetic (PK) studies in laboratory animals showed that CPX-POM is rapidly and 
completely metabolized to its active metabolite, CPX, which then disappears from plasma 
following systemic administration of CPX-POM.  Following systemic administration of 
CPX-POM, the dose is eliminated from the body via renal clearance of CPX and the inactive 
glucuronide metabolite of CPX (CPX-G).   


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In rats, intravenous (IV) CPX-POM administered for 28 consecutive days did not cause 
mortality or changes in body weight, food consumption, ophthalmology, hematology, 
coagulation, clinical chemistry, urinalysis, or organ weights.  There were no test item-related 
findings grossly or microscopically at the highest dose level tested (50 mg/kg/day).  Test 
item-related transient clinical signs, including slight to moderate decreased activity, increased 
respiration, eating-like behavior, and slight to moderate incoordination were noted 
immediately after dosing at 50 mg/kg/day.  The no observed adverse effect level (NOAEL) 
in rats was 25 mg/kg/day in males and 50 mg/kg/day in females.  
In dogs, CPX-POM administered for 28 consecutive days did not cause mortality or changes 
in body weight, food consumption, electrocardiogram (ECG) parameters, hematology, 
coagulation, clinical chemistry, urinalysis, or organ weights.  There were no test item-related 
findings grossly or microscopically at dose levels up to 30 mg/kg/day.  Test item-related 
transient clinical signs such as salivation, fecal changes, aggression, shaking, and tremors 
were noted after dosing at the highest dose level tested on the study (30 mg/kg/day).  
Convulsion was apparent in one dog on a single occasion.  Test-item related ophthalmic 
changes were noted in 3/10 dogs treated with 30 mg/kg/day.  Thus, the NOAEL in dogs was 
determined to be 10 mg/kg/day and the highest non-serious toxic dose (HNSTD) in the dog 
was determined to be 30 mg/kg.   
The starting dose of CPX-POM in patients was selected based on the results of the IV CPX-
POM 28-day Good Laboratory Practices (GLP) toxicology studies conducted in the rat and 
dog and consistent with FDA guidance (FDA, 2010) (see Section 4.4).   
CicloMed is aware of 2 published reports of CPX-O administered orally to humans (Minden 
et al, 2014; Kellner et al, 1981).  Following oral administration of CPX-O to patients with 
refractory hematologic malignancies, evidence of pharmacodynamic (PD) activity was 
observed (Minden et al, 2014; Song et al, 2011).  Administration by the oral route of 
administration, however, is not feasible because of dose-limiting gastrointestinal toxicity and 
poor oral bioavailability due to high first pass effect (Minden et al, 2014).   
The Investigator’s Brochure provides further details of the nonclinical studies and published 
clinical evaluations of CPX-POM (CPX-POM Investigator’s Brochure, 2017).  


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3. 
OBJECTIVES 
The primary objective of this study is: 
• To evaluate the dose limiting toxicities (DLTs) and maximum tolerated dose 
(MTD) of CPX-POM administered IV and establish the CPX-POM dose 
recommended for further investigation. 
The secondary objectives of this study are: 
• To characterize the plasma and urine PK of CPX-POM and its metabolites 
following single and multiple dose administration;  
• To identify preliminary anti-tumor activity of CPX-POM;  
• To determine urine β-glucuronidase activity in patients participating in the trial. 
The exploratory objectives of this study are: 
• To characterize the pharmacologic effects of CPX-POM on circulating biomarkers of 
Wnt and Notch cell signaling pathways; 
• To explore PD relationships between changes in circulating biomarkers and drug 
and/or metabolites exposure and other outcomes. 


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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a first-in-human, Phase 1, multicenter, open label, dose escalation study to evaluate 
the DLTs and MTD and to determine the recommended Phase 2 dose (RP2D) of CPX-POM 
administered IV in patients with any histologically- or cytologically-confirmed solid tumor 
type.  Secondary objectives include characterization of the safety and PK profile of 
CPX-POM and identification of preliminary anti-tumor activity in this patient population.  
Biomarkers and their relationship to PK and other outcomes will be examined as an 
exploratory objective. 
The study will initially employ an accelerated titration design, with a single patient enrolled 
in each cohort (i.e., Single-Patient Cohorts).  The initial patient cohort will receive 
CPX-POM at a starting dose of 30 mg/m2.  Doses will be escalated in 100% increments (i.e., 
doubling), until a ≥Grade 2 toxicity (with the exception of alopecia), as determined according 
to the United States (US) National Cancer Institute (NCI) Common Terminology Criteria for 
Adverse Events (CTCAE), version 4.03, is encountered, at which point that cohort and all 
subsequent cohorts will follow a classical “3 + 3” dose escalation design (i.e., standard 
cohorts).   
After each cohort is completed, a Safety Review Committee (SRC) comprised of the CRO 
Medical Monitor, Principal Investigator(s), and Sponsor representatives will meet to discuss 
the data and decide upon the next dose escalation.  Doses in the standard cohorts will be 
escalated in 25 to 50% increments, based on SRC decision, until the MTD is reached.  In 
addition, after completion of Cycle 1 for the first 4 to 6 patients, the SRC will review safety, 
PK, and PD data to determine if any changes to the dosing schedule are indicated. 
Intrapatient dose escalation will not be allowed in any patient at any time. 
Each patient in a dose cohort must have received at least 80% of their CPX-POM doses, 
unless due to toxicity, during Cycle 1 with follow-up safety evaluations through Day 22 (or 
Cycle 2, Day 1, if continuing in the study) to be eligible for the assessment of DLT.   
Patients may continue to receive cycles of CPX-POM until progression of disease, 
intolerable toxicity occurs, or another withdrawal criterion applies. 
Approximately 24 patients will be enrolled in the Single-Patient and Standard Dose 
Escalation Cohorts to establish the MTD.  In addition to these estimated 24 patients, 
Expansion Cohort(s) may be enrolled after the MTD is reached to either explore different 
dosing schedules, increase the experience with a particular tumor type (e.g., muscle invasive 


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bladder cancer [MIBC]), or to examine the safety and anti-tumor activity of CPX-POM in 
combination with certain other anticancer agents.   
All patients are to attend a Follow-up Visit 28 days (± 5 days) after the last study drug dose.  
No follow-up after completion of the Follow-up Visit is planned, with the exception of 
monitoring of ongoing treatment-emergent adverse events (AEs) until resolution or until the 
AE is clearly determined to be due to a patient’s stable or chronic condition or intercurrent 
illness(es). 
Dose escalation procedures will be conducted as shown in Table 2. For further details and 
example doses, see Section 4.2. 
Table 2. 
Dose Escalation Procedures 
Accelerated Titration (Single-Patient Cohorts; n=1 each) 
No ≥Grade 2 AEs 
• Continue evaluation of single-patient dose cohorts. 
• Escalate by 100% to next dose level. 
At least 1 ≥Grade 2 AE not 
meeting the definition of 
DLT 
• Expand current and subsequent cohorts to at least 3 patients (see 
Standard Dose Escalation Scheme below). 
1 DLT  
• Expand current cohort up to 6 patients or until 2 DLTs are 
encountered (Standard Dose Escalation Scheme below). 
Standard Dose Escalation (Standard Cohorts; n=3 to 6 each) 
No DLT 
• Escalate by 25−50% to next dose level. 
1 DLT in ≤3 patients 
• Expand cohort up to 6 patients. 
1 DLT in 6 patients 
• Escalate by 25−50% to next dose level. 
> 1 DLT in ≤ 6 patients 
• MTD reached; stop dose escalation.   
• Possibly explore intermediate doses for the RP2D. 
 
Abbreviations:  AE = adverse event; DLT = dose limiting toxicity; MTD = maximum tolerated dose; RP2D = 
recommended Phase 2 dose. 
 


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A Dose-Limiting Toxicity will be defined as any of the following, if deemed related to study 
drug: 
• Grade 4 thrombocytopenia of any duration  
• Grade 3 thrombocytopenia with significant hemorrhage of any duration  
• Grade 4 absolute neutrophil count (ANC) greater than 5 days  
• Febrile neutropenia  
• Grade ≥3 non-hematologic toxicity of any duration, except:  
o Grade 3 nausea, vomiting, or diarrhea and Grade 4 vomiting or diarrhea in the 
absence of maximal medical therapy that resolves in 72 hours  
o Grade 3 fatigue lasting <5 days 
o Grade 3 hypertension that can be controlled with medical therapy 
o An increase of indirect (unconjugated) bilirubin indicative of 
M. Meulengracht/Gilbert’s syndrome 
o Serum lipase and/or serum amylase CTCAE Grade 3 ≤7 consecutive days 
without clinical signs or symptoms of pancreatitis  
• Delay in study drug due to toxicity for >2 weeks   
• alanine aminotransferase (ALT)/aspartate aminotransferase (AST) >3x the upper limit 
of normal (ULN) with bilirubin >2xULN without another explanation (e.g., 
cholestasis)  
• Any patient who is unable to receive 80% of the expected doses of CPX-POM (i.e., 
patients who are unable to receive at least 4 of the 5 scheduled doses) in Cycle 1 
because of AEs will be considered to have a DLT. 
4.2. 
Planned Doses for Dose Escalation 
As described in Sections 4.1, 4.4, and 6.1.4, the starting dose for this study will be 30 mg/m2 
as a 10-minute IV infusion once daily for 5 days, repeated every 21 days.  As stated in 
Section 4.1, the study will initially adopt an accelerated titration design until ≥Grade 2 
toxicity is encountered.  Therefore, as an example, if the first ≥Grade 2 toxicity is not seen 
before the 120 mg/m2 dose level in the early cohorts, then the doses shown in Table 3 may be 
administered.  


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Table 3. 
Example Doses for Accelerated Titration Cohorts 
Cohort 
Daily Dose (mg/m2) 
Number of Patients 
1 
30* 
1 
2 
60 
1 
3 
120 
1 
X 
Until ≥ Grade 2 toxicity 
* In the unlikely event of a DLT at this low dose, up to 5 more patients would be accrued at this dose.  If >1 
DLT was experienced at this dose, a LOWER dose of 15 mg/m2 would be explored in a further cohort. 
Once ≥Grade 2 toxicity is encountered, the standard dose escalation scheme (“3 + 3”) will 
apply and dose escalations will proceed in 25 to 50% increments, although these increments 
may be modified by discussion with the SRC, according to toxicity or other data accrued in 
preceding cohorts.  If, for example, the first ≥Grade 2 toxicity occurs at the 240 mg/m2 dose 
level, the doses shown in Table 4 may be administered.  These doses are EXAMPLES and 
not absolutes until all data from patients in preceding cohorts have been discussed with the 
Principal Investigators and the SRC.  Dose increments generally will be smaller as the MTD 
is thought to be approaching.  
Table 4. 
Example Doses for Standard Dose Escalation Cohorts 
Cohort 
Daily Dose (mg/m2) 
Dose Increase 
Number of Patients 
4 
240 
 
3 - 6 
5 
350  
46% 
3 - 6 
6 
475 
36% 
3 - 6 
X 
? 600  
26% 
3 - 6 
 
All SRC discussions and decisions will be documented and patient safety will be the 
paramount concern. 
4.3. 
Rationale for Study Design 
The primary objective of this study is to determine the MTD of CPX-POM in cancer patients 
with advanced solid tumors.  This information will be used to inform the selection of the 
CPX-POM dose to be used in future studies.   
The proposed study design approach is to use a single patient accelerated dose escalation 
until Grade ≥2 toxicity is observed, followed by a conventional 3+3 design in order to 
determine the MTD.  In view of prior human clinical experience with systemic exposure to 
CPX, the use of an accelerated, single patient dose escalation scheme in order to minimize 
patient exposure to suboptimal doses of CPX-POM is warranted. 


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4.4. 
Dose Selection 
Food and Drug Administration guidelines (FDA, 2010) were employed to determine the 
starting dose for this study, 30 mg/m2.  As described in this guidance, a common approach 
for determining a starting dose for small molecule drugs is to use one-tenth the severely toxic 
dose in 10% of the animals (STD10) in rodents OR one-sixth the highest non-severely toxic 
dose (HNSTD) in non-rodents.  In GLP toxicology studies in rats, the CPX-POM STD10 was 
not reached, so the highest dose tested (50 mg/kg) was used to determine a safe human 
starting dose of 30 mg/m2  (one-tenth the STD10 based on mg/m2).  In GLP toxicology 
studies in dogs, the CPX-POM HNSTD was 10 mg/kg based on tremors and convulsion 
observed at 30 mg/kg.  One-sixth of the HNSTD observed in dogs, converted to mg/m2, also 
supports a starting dose of 30 mg/m2 in patients.  
4.5. 
End of Study Definition 
A patient is considered to have completed the study if he/she has completed the first cycle of 
the study.   
The end of the study is defined as the date of the last procedure for the last patient in the 
study.  At the end of the study the patient will complete the D22 visit as well as the Follow-
Up Visit. 


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5. 
STUDY POPULATION 
5.1. 
Inclusion Criteria 
Patients must meet all of the following inclusion criteria to be eligible for participation in this 
study. 
1. Patient has histologically- or cytologically- confirmed metastatic or advanced-stage 
solid malignant tumor that is refractory to standard therapy.  Patients should only be 
included if no therapy exists or if they have received all standard therapies that would 
be potentially curative or might provide significant benefit.  
2. Patient may have received up to 4 prior lines of cytotoxic chemotherapy or 
immunotherapy for their metastatic disease (e.g., docetaxel + doxorubicin ± 
cyclophosphamide), and also may have received additional prior endocrine therapy, 
as appropriate (e.g., for breast or prostate cancer), or non-myelosuppressive therapy 
(e.g., bevacizumab, trastuzumab). 
3. Patient has experienced progressive disease during or following or was intolerant of 
their most recent treatment regimen.  Supporting information about prior progressive 
disease will be collected, if available. 
4. Patient is male or female aged ≥18 years. 
5. Patient provided signed and dated informed consent prior to initiation of any study 
procedures. 
6. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 
(fully active, able to carry out all pre-disease activities without restriction) or 1 
(unable to perform physically strenuous activity but ambulatory and able to carry out 
work of a light or sedentary nature). 
7. Patient has a predicted life expectancy of ≥3 months. 
8. Patient has adequate renal function (creatinine ≤1.5 × ULN) or a GFR of ≥50 
mL/min). 
9. Patient has adequate hepatic function, as evidenced by a total bilirubin ≤1.5 × ULN, 
AST, and /or ALT ≤3 × ULN or ≤5 ×ULN, if due to liver involvement by tumor. 
10. Patient has adequate bone marrow function, as evidenced by hemoglobin ≥9.0 g/dL in 
the absence of transfusion within the previous 72 hours, platelet count 
≥100×109cells/L, and ANC ≥1.5×109 cells/L. 


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11. Patient has no significant ischemic heart disease or myocardial infarction within 6 
months before the first dose of CPX-POM and currently has adequate cardiac 
function, as evidenced by a left ventricular ejection fraction of >50% as assessed by 
multi-gated acquisition (MUGA) or ultrasound/echocardiography (ECHO); and 
corrected QT interval (QTc) <470 msec by Fridericia (QTcF).  The eligibility of 
patients with ventricular pacemakers for whom the QT interval may not be accurately 
measurable will be determined on a case-by-case basis by the Sponsor in consultation 
with the Medical Monitor. 
12. Patient and his/her partner agree to use adequate contraception after providing written 
informed consent through 3 months after the last dose of CPX-POM, as follows: 
a. For women:  Negative pregnancy test during Screening and at Day 1 of each 
treatment cycle and compliant with a medically-approved contraceptive 
regimen during and for 3 months after the treatment period or documented to 
be surgically sterile or postmenopausal. 
b. For men:  Compliant with a medically-approved contraceptive regimen during 
and for 3 months after the treatment period or documented to be surgically 
sterile.  Men whose sexual partners are of child-bearing potential must agree 
to use 2 methods of contraception prior to study entry, during the study, and 
for 3 months after the treatment period. 
13. Patient is willing and able to participate in the study and comply with all study 
requirements. 
For the expansion cohort(s) of the study ONLY, if needed: 
14. Patient has a specific tumor-type and histology (e.g., locally advanced or metastatic 
bladder cancer), as designated by the Sponsor based on nonclinical and clinical data 
obtained prior to enrollment in the Expansion Cohort. 
15. Patient has measurable disease, as determined by the Investigator using the Response 
Evaluation Criteria for Solid Tumors (RECIST), version 1.1 (see Appendix 1). 
5.2. 
Exclusion Criteria 
Patients who meet any of the following exclusion criteria are not to be enrolled in this study. 
1. Patient has a history of risk factors for torsade de pointes (e.g., heart failure, 
hypokalemia, family history of long QT syndrome) or requires the use of concomitant 
medications that prolong the QT/QTc interval during study participation.  


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2. Patient has an abnormal cardiac appearance/heart size, as evidenced by chest X-ray or 
computed tomography (CT) scan. 
3. Patient has an uncontrolled or severe intercurrent medical condition (including 
uncontrolled brain metastases).  Patients with stable brain metastases either treated or 
being treated with a stable dose of steroids/anticonvulsants, with no dose change 
within 4 weeks before the first dose of CPX-POM and no anticipated dose change, 
are allowed.  The decision to exclude a patient from the study for an uncontrolled or 
severe intercurrent medical condition will be made by the Principal Investigator.  
Examples could include epilepsy, resistant infection, or any other neurological 
disease that would make clinical assessment difficult. 
4. Patient underwent major surgery within 4 weeks before the first dose of CPX-POM or 
received cancer-directed therapy (chemotherapy, radiotherapy, hormonal therapy, 
biologic or immunotherapy, etc.) or an investigational drug or device within 4 weeks 
(6 weeks for mitomycin C and nitrosoureas) or 5 half-lives of that agent (whichever is 
shorter) before the first dose of CPX-POM.  A minimum of 10 days between 
termination of the investigational drug and administration of CPX-POM is required.  
In addition, any drug-related toxicity, with the exception of alopecia, should have 
recovered to ≤Grade 1. 
5. If female, patient is pregnant or breast-feeding. 
6. Patient has evidence of a serious active infection (e.g., infection requiring treatment 
with IV antibiotics). 
7. Patient has active Hepatitis A infection.  
8. Patient known human immunodeficiency virus (HIV) or Hepatitis B or C infection, as 
such patients may be at increased risk for toxicity due to concomitant treatment and 
disease-related symptoms may preclude accurate assessment of the safety of 
CPX-POM. 
9. Patient has an important medical illness or abnormal laboratory finding that, in the 
Investigator’s opinion, would increase the risk of participating in this study. 
10. Patient is taking warfarin.  
11. Patient has a history of other malignancy treated with curative intent within the 
previous 5 years with the exception of adequately treated non-melanoma skin cancer 
or carcinoma in situ of the cervix. Patients with previous invasive cancers are eligible 
if the treatment was completed more than 5 years prior to initiating current study 
treatment, and there is no evidence of recurrent disease. 


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12. Patient has known allergy or hypersensitivity to components of CPX-POM. 
13. Patient is taking any iron replacement therapy administered IV, IM, or orally due to 
the potential for loss of anticancer activity due to ciclopirox (the active metabolite of 
CPX-POM) chelating iron. 
5.3. 
Meals and Dietary Considerations 
On Days 1 and 5 of Cycle 1, patients will be required to stay at the clinical research unit for 
at least 12 hours for PK sampling and other assessments.  Patients will be encouraged to 
drink eight 8-oz glasses of water over a 24-hour period, i.e., 64 oz. total.   
If Day 5 Cycle 1 steady state PK assessments are postponed to Day 5 of Cycle 2, the 
considerations described above will also be postponed to Day 5 of Cycle 2.   
5.4. 
Screen Failures 
Patients who fail inclusion and/or exclusion criteria may not be rescreened for the study. 


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6. 
TREATMENTS 
6.1. 
Investigational Product 
6.1.1. 
Description of Investigational Product 
CPX-POM prodrug, sodium ((6-cyclohexyl-4-methyl-2-oxopyridin-1(2H)-yl) oxy) methyl 
phosphate, is the phosphoryloxymethyl ester of CPX.  CPX-POM will be provided as a 
sterile liquid formulation for IV administration. 
6.1.2. 
Packaging and Labeling 
CPX-POM will be packaged in plastic, 10-mL vials containing CPX-POM 50 mg/mL 
solution.  Vials will be labeled according to applicable regulatory requirements.   
6.1.3. 
Storage and Handling 
CPX-POM vials must be stored under refrigerated conditions at 2 to 8 ºC.   
Only patients enrolled in the study may receive CPX-POM and only authorized site staff may 
supply or administer CPX-POM.  All CPX-POM must be stored in a secure, environmentally 
controlled, and monitored (manual or automated) area in accordance with the labeled storage 
conditions with access limited to the investigator and authorized site staff. 
6.1.4. 
Dosage and Administration 
CPX-POM will be administered as an IV infusion once daily on Days 1-5 of each 21-day 
treatment cycle.  CPX-POM will be added to a 100 mL piggyback bag of 0.9% sodium 
chloride solution and infused over a 10-minute period.  The initial dose for the first patient 
enrolled (i.e., Cohort 1) will be 30 mg/m2.   
At baseline, the body surface area (BSA) will be calculated by the Dubois method using 
Screening height and baseline weight measurements.  The baseline BSA is to be used to 
determine the patient’s study drug dose.  Thereafter, BSA is to be recalculated on Day 1 of 
every other treatment cycle, starting with Cycle 3, and the patient’s study drug dose adjusted 
accordingly. 
Dubois Formula:  BSA= 0.007184 x W0.425 x H0.725 
The dose escalation procedure is described in Section 4, and further details and example 
doses are shown in Section 4.2. 


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After completion of Cycle 1 for the first 4 to 6 patients, the SRC will review safety, PK, and 
PD data to determine if any changes to the dosing schedule are indicated (e.g., adding an 
additional 5 days of dosing to each treatment cycle). 
6.1.5. 
Dose Modifications 
If a patient develops a DLT, CPX-POM dosing should be discontinued until the toxicity is 
resolved (see definition of a DLT in Section 4).  If the toxicity resolves to at least Grade 1, 
treatment may be re-initiated and the dose of CPX-POM should be reduced by one dose 
level.  If a patient has a second episode of the same DLT despite dose reduction, they should 
be permanently discontinued from study.  
6.1.6. 
Compliance 
Administration of CPX-POM will be performed by site personnel.  Compliance will be 
assessed by inspection of drug accountability records at the study site.  
6.1.7. 
Accountability 
The investigator or designee (i.e., pharmacist) is responsible for ensuring adequate 
accountability of all used and unused investigational medicinal product, placebos, and 
comparators.  This includes acknowledgment of receipt of each shipment of investigational 
product (quantity and condition), patient dispensing records, and returned or destroyed study 
product.  Dispensing records will document quantities received from CicloMed and 
quantities administered to patients, including lot number, date dispensed/administered, 
patient identifier number, and the initials of the person dispensing/administering the 
medication. 
At study initiation, the monitor will evaluate the site’s standard operating procedure for 
investigational medicinal product disposal/destruction in order to ensure that it complies with 
CicloMed requirements.  Drug may be returned or destroyed on an ongoing basis during the 
study, if appropriate.  At the end of the study, following final drug inventory reconciliation 
by the monitor, the study site will dispose of and/or destroy all unused investigational 
medicinal product supplies, including empty containers, according to these procedures.  If the 
site cannot meet CicloMed’s requirements for disposal, arrangements will be made between 
the site and CicloMed or its representative for destruction or return of unused investigational 
medicinal product supplies. 
All drug supplies and associated documentation will be periodically reviewed and verified by 
the study monitor over the course of the study.   
Further guidance and information for the final disposition of unused investigational product 
is provided in the Study Procedures Manual. 


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6.2. 
Prior and Concomitant Medications 
Medications taken within 30 days before baseline (Study Visit 2) must be recorded as prior 
medications.   
Prohibited concomitant medications include any anti-cancer agents, steroids (except stable 
doses being taken for brain metastases), any iron replacement therapy, warfarin, or any drug 
known to have significant nephrotoxicity.  A minimum of 10 days between termination of the 
prohibited concomitant medications or a duration of five elimination half-lives will be 
required prior to administration of IV CPX-POM to eligible patients.  Radiation therapy is 
also prohibited.   
All concomitant medications will be recorded from the time of Screening through the 
Follow-up Period. 


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7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PATIENT DISCONTINUATION/WITHDRAWAL  
7.1. 
Discontinuation of Study Treatment 
Treatment should be discontinued for a DLT until the toxicity is resolved.  If treatment is 
reinitiated, then the dose of CPX-POM should be reduced as described in Section 6.1.5.  If a 
patient has a second episode of the same DLT despite dose reduction, he or she should be 
removed from study as outlined in Table 1. Schedule of Assessments (complete D22 and the 
Early Termination Visit). 
In the event of discontinuation of CPX-POM, every effort should be made to complete the 
assessments that are scheduled for the Follow-up/Early Termination visit.  See the Schedule 
of Assessments (Table 1) for data to be collected at the time of early termination. 
7.2. 
Patient Discontinuation/Withdrawal from the Study 
A patient may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, compliance, 
or administrative reasons. 
If the patient withdraws consent for disclosure of future information, the Sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. 
If a patient withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the investigator must document this in the site study records. 
If a patient withdraws prematurely from the trial for any reason, study staff should make 
every effort to complete the full set of evaluations scheduled for the Follow-up/Early 
Termination visit. See the Schedule of Assessments (Table 1) for data to be collected at the 
time of early termination. 
7.3. 
Lost to Follow Up 
A patient will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  
The following actions must be taken if a patient fails to return to the clinic for a required 
study visit: 
• The site must attempt to contact the patient and reschedule the missed visit as soon as 
possible and counsel the patient on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the patient wishes to and/or should continue in the 
study. 


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• Before a patient is deemed lost to follow up, the investigator or designee must make 
every effort to regain contact with the patient (where possible, 3 telephone calls and, if 
necessary, a certified letter to the patient’s last known mailing address or local equivalent 
methods).  These contact attempts should be documented in the patient’s medical record. 
• Should the patient continue to be unreachable, he/she will be considered to have 
withdrawn from the study.  


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8. 
STUDY ASSESSMENTS 
8.1. 
Cancer Evaluation 
All patients will undergo a cancer evaluation to include determination of staging and 
metastases for screening purposes.  Disease response assessments will be performed for 
patients with measurable disease within 28 days prior to the first dose of CPX-POM and 
repeated before the first study drug dose (Day 1) of every second cycle (i.e., at approximately 
6-week intervals).  If a patient with measurable disease discontinues from the study after 
6 weeks and before a disease response assessment is scheduled, an additional assessment 
may be performed, upon consultation with the Sponsor, at the end of treatment (i.e., on 
approximately Day 22 of the last cycle).   
For the screening assessments, all sites of disease will be imaged by CT, if possible.  If the 
anatomic region cannot be adequately imaged by CT, magnetic resonance imaging (MRI) 
may be used instead.  Subsequent assessments should use the same radiographic methods as 
used during Screening.  Disease response will be assessed by the investigator using RECIST, 
version 1.1 (Eisenhauer et al, 2009; see Appendix 1).  Tumor markers applicable to the 
patient’s solid tumor type (e.g., prostate-specific antigen [PSA] for prostate cancer; cancer 
antigen-125 [CA-125] in ovarian cancer; carcinoembryonic antigen [CEA] in colorectal or 
pancreatic cancer, cancer antigen 19-9 [CA-19-9] in pancreatic cancer) will also be measured 
within ±2 days of tumor measurements. 
8.2. 
Safety Assessments 
8.2.1. 
Adverse Events and Serious Adverse Events 
8.2.1.1. 
Definitions 
Adverse Event 
An AE is any untoward medical occurrence in a clinical investigation subject administered a 
medicinal product and which does not necessarily have a causal relationship with this 
treatment.  An AE can therefore be any unfavorable and unintended sign, symptom, or 
disease temporally associated with the use of a medicinal product, whether or not considered 
related to the medicinal product. 
AEs also include the following: 
• Pre- or post-treatment complications that occur as a result of protocol mandated 
procedure (e.g. such as venipuncture, biopsy) during or after Screening (before the 
administration of study investigational medicinal product). 


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• Any pre-existing condition that increases in severity, or changes in nature during or as a 
consequence of the study investigational medicinal product phase of a human clinical 
trial, will also be considered an AE. 
• Complications and termination of pregnancy (see Section 8.2.2for additional information) 
• All AEs that occur from the study screening visit onwards and throughout the duration of 
the study, including the follow-up off study medication period should be recorded as an 
AE. 
An AE does not include the following: 
• Medical or surgical procedures (e.g., surgery, endoscopy, tooth extraction, transfusion) 
performed; the condition that leads to the procedure is an AE. 
• Pre-existing diseases or conditions or laboratory abnormalities present or detected before 
the screening visit that do not worsen.  
• If progression of underlying malignancy is clearly consistent with the suspected 
progression of the underlying cancer as defined by RECIST 1.1, or with clinical 
symptoms (clinical progression), it should not be reported as an AE/SAE.  Similarly, 
hospitalization due exclusively to the progression of underlying malignancy should NOT 
be reported as an SAE. 
• Situations where an untoward medical occurrence has not occurred (e.g., hospitalization 
for elective surgery, social and/or convenience admissions). 
• Any medical condition or clinically significant laboratory abnormality with an onset date 
before the consent form is signed and not related to a protocol-associated procedure is not 
an AE.  It is considered to be pre-existing and should be documented on the medical 
history CRF. 
• Uncomplicated pregnancy. 
• An induced elective abortion to terminate a pregnancy without medical reason. 
• "Lack of efficacy" or "failure of expected pharmacological action" per se will not be 
reported as an AE or SAE.  However, the signs, symptoms, and/or clinical sequelae 
resulting from lack of efficacy may be reported as AE or SAE if they fulfill the definition 
of an AE or SAE. 
Serious Adverse Event 
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease). 
A SAE is defined as any untoward medial occurrence that, at any dose: 


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• Results in death 
• Is life-threatening.  The term 'life-threatening' in the definition of 'serious' refers to an 
event in which the patient was at risk of death at the time of the event. It does not refer to 
an event, which hypothetically might have caused death, if it were more severe. 
• Requires inpatient hospitalization or prolongation of existing hospitalization.  In general, 
hospitalization signifies that the patient has been detained (usually involving at least an 
overnight stay) at the hospital or emergency ward for observation and/or treatment that 
would not have been appropriate in the physician’s office or outpatient setting. 
Complications that occur during hospitalization are AEs. If a complication prolongs 
hospitalization or fulfills any other serious criteria, the event is serious. When in doubt as 
to whether “hospitalization” occurred or was necessary, the AE should be considered 
serious.  Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE. 
• Results in persistent disability/incapacity.  The term disability means a substantial 
disruption of a person’s ability to conduct normal life functions.  This definition is not 
intended to include experiences of relatively minor medical significance such as 
uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma 
(e.g., sprained ankle) which may interfere with or prevent everyday life functions but do 
not constitute a substantial disruption. 
• Is a congenital anomaly/birth defect in the offspring of a subject who received 
investigational medicinal product. 
• Other situations.  Medical or scientific judgment should be exercised in deciding whether 
SAE reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but may 
jeopardize the patient or may require medical or surgical intervention to prevent one of 
the other outcomes listed in the above definition. These events should usually be 
considered serious.  Examples of important medical events include invasive or malignant 
cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, 
blood dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse. 
8.2.1.2. 
Time Period and Frequency for Collecting Adverse Event and Serious 
Adverse Event Information  
All AEs and SAEs will be collected from the signing of the informed consent form (ICF) 
through the Follow-up visit.   
Medical occurrences that begin before the start of study intervention but after obtaining 
informed consent will be recorded on the Medical History/Current Medical Conditions 
section of the CRF not the AE section. 


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Investigators are not obligated to actively seek AE or SAE after conclusion of the study 
participation. However, if the investigator learns of any SAE, including a death, at any time 
after a patient has been discharged from the study, and he/she considers the event to be 
reasonably related to the study intervention or study participation, the investigator must 
promptly notify the Sponsor. 
8.2.1.3. 
Method of Detecting Adverse Events and Serious Adverse Events 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the patient is the preferred method to inquire about 
AE occurrences. 
8.2.1.4. 
Regulatory Reporting Requirements for Serious Adverse Events 
Prompt notification (within 24 hours from the first time a site team member is made aware of 
the event) by the investigator to the Sponsor of a SAE is essential so that legal obligations 
and ethical responsibilities towards the safety of patients and the safety of a study 
intervention under clinical investigation are met.  
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, Institutional Review Boards (IRB), and investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and Sponsor policy and 
forwarded to investigators as necessary. 
An investigator who receives an investigator safety report describing a SAE or other specific 
safety information (e.g., summary or listing of SAEs) from the Sponsor will review and then 
file it along with the Investigator’s Brochure and will notify the IRB, if appropriate according 
to local requirements. 
8.2.1.5. 
Reporting Procedures 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory reports, and diagnostics reports) 
related to the event.  The investigator will then record all relevant AE/SAE information in the 
CRF. 
It is not acceptable for the investigator to send photocopies of the patient’s medical records in 
lieu of completion of the AE/SAE CRF page.  There may be instances when copies of 
medical records for certain cases are requested by CicloMed or its designee.  In this case, all 


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patient identifiers, with the exception of the patient number, will be redacted on the copies of 
the medical records before submission. 
The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information.  Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE. 
All SAEs will be recorded and reported to the Sponsor or their designee within 24 hours from 
the time any site team member is made aware of the event.  The investigator will submit any 
updated SAE data to the Sponsor within 24 hours of it being available.  If any part of the 
source providing details of the event is not available, the Investigator will submit the SAE 
with as much information as he/she has at the time of the reporting requirements. 
Contacts and procedures for SAE reporting can be found in the Study Procedures Manual.   
8.2.1.6. 
Assessment of Causality 
The investigator is obligated to assess the relationship between CPX-POM and each 
occurrence of each AE/SAE as follows:  
• There is a "reasonable possibility" of a relationship between the CPX-POM and the AE.  
This conveys that there are facts, evidence, and/or arguments to suggest a causal 
relationship, rather than a relationship cannot be ruled out. 
• There is not a “reasonable possibility” of a relationship between CPX-POM and the AE. 
The investigator will use clinical judgment to determine the relationship.  Alternative causes, 
such as underlying disease(s), concomitant therapy, and other risk factors, as well as the 
temporal relationship of the event to study intervention administration will be considered and 
investigated.  The investigator will also consult the Investigator’s Brochure (IB) in his/her 
assessment. 
For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to the Sponsor or contract research organization 
(CRO). However, it is very important that the investigator always make an assessment of 
causality for every event before the initial transmission of the SAE data to the Sponsor or 
CRO.  The investigator may change his/her opinion of causality in light of follow-up 
information and send a SAE follow-up report with the updated causality assessment. 
The causality assessment is one of the criteria used when determining regulatory reporting 
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The relationship to study procedures (e.g., invasive procedures such as venepuncture or 
biopsy) should also be assessed using the following considerations: 
• There is a reasonable possibility that the AE occurred as a result of protocol-mandated 
procedures such as venipuncture or biopsy. 
• There is not a reasonable possibility that the AE occurred as a result of a protocol-
mandated procedure.   
8.2.1.7. 
Assessment of Intensity 
The investigator will make an assessment of intensity (Grade) for each AE and SAE reported 
during the study, using as a guide the NCI CTCAE, as provided in the Study Procedures 
Manual.   
8.2.1.8. 
Follow-up of Adverse Events and Serious Adverse Events 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by CicloMed or its 
designee to elucidate the nature and/or causality of the AE or SAE as fully as possible. This 
may include additional laboratory tests or investigations, histopathological examinations, or 
consultation with other health care professionals. 
If a patient dies during participation in the study or during a recognized follow-up period, the 
investigator will provide CicloMed or its designee with a copy of any post-mortem findings 
including histopathology.   
New or updated information will be recorded in the originally completed CRF. 
The investigator will submit any updated SAE data to the Sponsor within 24 hours of receipt 
of the information.  Contacts for SAE reporting can be found in the Study Procedures 
Manual. 
8.2.2. 
Pregnancy 
Pregnancies in female patients and female partners of male patients will be recorded from 
after the start of study intervention until 30 days after the last dose.  All pregnancies must be 
followed to conclusion to determine outcomes for both mother and baby.   
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy will be reported as an AE or SAE.  A spontaneous 
abortion is always considered to be an SAE and will be reported as such.  Any post-study 
pregnancy-related SAE considered reasonably related to the study intervention by the 
investigator will be reported to the Sponsor as described in Sections 8.2.1.4 and 8.2.1.5.  


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While the investigator is not obligated to actively seek this information in former study 
patients, he or she may learn of an SAE through spontaneous reporting.  
8.2.2.1. 
Male Patients with Partners who Become Pregnant 
The investigator will attempt to collect pregnancy information on any male patient’s female 
partner who becomes pregnant while the male patient is in this study. This applies only to 
male patients who receive CPX-POM. 
After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the investigator will record pregnancy information on the appropriate form and 
submit it to the Sponsor within 24 hours of learning of the partner’s pregnancy.  The female 
partner will also be followed to determine the outcome of the pregnancy.  Information on the 
status of the mother and child will be forwarded to the Sponsor.  Generally, the follow-up 
will be no longer than 6 to 8 weeks following the estimated delivery date.  Any termination 
of the pregnancy will be reported regardless of fetal status (presence or absence of 
anomalies) or indication for the procedure.  
8.2.2.2. 
Female Patients who Become Pregnant  
The investigator will collect pregnancy information on any female patient who becomes 
pregnant while participating in this study.  Information will be recorded on the appropriate 
form and submitted to the Sponsor within 24 hours of learning of a patient's pregnancy. The 
patient will be followed to determine the outcome of the pregnancy.  The investigator will 
collect follow-up information on the patient and the neonate and the information will be 
forwarded to the Sponsor.  Generally, follow-up will not be required for longer than 6 to 
8 weeks beyond the estimated delivery date.  Any termination of pregnancy will be reported, 
regardless of fetal status (presence or absence of anomalies) or indication for the procedure. 
Any female patient who becomes pregnant while participating in the study will discontinue 
CPX-POM and be withdrawn from the study.  
8.2.3. 
Other Safety and Screening Assessments 
8.2.3.1. 
Cardiac Evaluation 
Patients will undergo a cardiac evaluation at Screening using MUGA or ECHO to evaluate 
their eligibility to participate in the study. 
Patients will also undergo a chest X-ray or CT scan to confirm normal cardiac 
appearance/heart size at Screening.  


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8.2.3.2. 
Eastern Cooperative Oncology Group 
Patients will be evaluated for ECOG performance status at Screening and Follow-Up to 
evaluate their eligibility to participate in the study.  The ECOG performance status grades 
and criteria are shown in Table 5. 
Table 5. 
Eastern Cooperative Performance Status  
GRADE 
ECOG PERFORMANCE STATUS 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of 
a light or sedentary nature, e.g., light house work, office work 
2 
Ambulatory and capable of all selfcare but unable to carry out any work activities; up 
and about more than 50% of waking hours 
3 
Capable of only limited selfcare; confined to bed or chair more than 50% of waking 
hours 
4 
Completely disabled; cannot carry on any selfcare; totally confined to bed or chair 
5 
Dead 
*Oken M, Creech R, Tormey D, et al. Toxicity and response criteria of the Eastern Cooperative Oncology 
Group. Am J Clin Oncol. 1982;5:649-655. 
 
8.2.3.3. 
Physical Examinations 
A complete physical examination will be conducted at Screening and Follow-up.  At each 
other study visit, patients will be assessed for continued dosing and any possible 
symptoms/toxicities and a physical examination may be performed, if indicated (see 
Schedule of Assessments, [Table 1]).  Body weight should be measured at each study visit.  
Height should be measured at Screening. 
8.2.3.4. 
Vital Signs 
Vital signs will include blood pressure, respiratory rate, pulse, oxygen saturation, and 
temperature and will be measured at the times and days shown in the Schedule of 
Assessments (Table 1).   


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Vital signs will be measured before any blood draws or injections scheduled for the same 
time point.   
8.2.3.5. 
Electrocardiograms and Holter Monitoring 
At Screening, 12-lead ECGs will be performed in triplicate, with each measurement 
separated by 2 minutes.  The average of the 3 screening ECGs will be used to calculate QTc 
and QTcF (Fridericia’s formula):  
 
to determine study eligibility.  Thereafter, single 12-lead ECGs will be performed at the dates 
and times indicated in the Schedule of Assessments (Table 1).   
On Day 1 of Cycle 1, digital Holter monitoring will be performed from 45 minutes pre-dose 
through 24 hours post-dose in order to examine any potential QTc changes and relate those, 
if present, to simultaneously obtained blood samples for plasma drug and/or metabolite 
concentration determination.  ECG extractions of the continuous Holter recordings will be 
performed at 45, 30, and 15 minutes pre-dose and at specific post-dose time points coinciding 
with the serial blood sampling time points for PK.  Patients will be instructed to assume a 
supine position 5 to 10 minutes prior to each serial blood sampling time point and remain 
supine throughout the 5-minute ECG extraction period just prior to serial blood sample 
collection.  During the 24-hour Holter monitoring period, a 12-lead ECG tracing may be 
printed out at any time while the patient is in the clinic at the discretion of the investigator.   
If for any reason Holter monitoring is not performed in conjunction with the PK sampling on 
Day 1 or the tracings are of poor quality, Holter monitoring may be performed in conjunction 
with the PK sampling on Day 5.   
8.2.3.6. 
Clinical Laboratory Assessments 
All protocol-required laboratory assessments, including hematology (including complete 
blood count), clinical chemistry (including comprehensive metabolic panel), thyroid panel, 
coagulation testing, and urinalysis must be conducted in accordance with the Study 
Procedures Manual and the Schedule of Assessments (Table 1). 
Abnormal laboratory tests that are clinically significant should also be recorded as AEs on 
the CRF, or as medical history if noted during Screening. 
A listing of clinical laboratory tests to be performed is provided in Table 6.   


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Table 6. 
Listing of Required Screening and Safety Laboratory Parameters 
Laboratory 
Assessments 
Parameters 
Hematology 
(CBC with 
differential) 
• 
Hemoglobin 
• 
Hematocrit  
• 
Platelet count 
• 
RBC count 
• 
Reticulocytes 
WBC Count with Differential 
• 
Neutrophils 
• 
Lymphocytes 
• 
Monocytes 
• 
Eosinophils 
• 
Basophils 
Clinical 
Chemistry 
(including CMP) 
• 
Potassium 
• 
Sodium 
• 
Chloride 
• 
Glucose  
• 
BUN 
• 
Creatinine  
• 
Creatinine 
clearance 
• 
ALP 
• 
ALT 
• 
AST 
• 
GGT 
• 
Alkaline 
phosphatase 
• 
Direct bilirubin 
• 
Indirect bilirubin 
• 
Total bilirubin 
• 
Total protein  
• 
Albumin 
• 
Calcium 
• 
Bicarbonate  
• 
Magnesium 
• 
Phosphate 
• 
Lipase 
• 
Amylase 
Coagulation  
• 
PT 
• 
aPTT 
 
Thyroid Panel  
• 
TSH 
• 
Free T4 
• 
Free and total T3 
Routine 
Urinalysis 
• 
Color 
• 
Turbidity 
• 
pH 
• 
Specific gravity 
• 
Glucose 
• 
Ketones 
• 
Nitrites 
• 
Bilirubin 
• 
Urobilirubin 
• 
Protein 
• 
RBCs 
• 
WBCs 
• 
Epithelial cells 
• 
Casts 
• 
Crystals 
• 
Bacteria 
• 
eGFR (Screening 
only) 
Other  
• 
Serum or urine 
hCG pregnancy 
test (for women of 
child bearing 
potential) 
• 
HIV (Screening 
only) 
• 
Hepatitis A 
(Screening only) 
• 
Hepatitis B 
(Screening only) 
• 
Hepatitis C 
(Screening only) 
Abbreviations:  ALP = alkaline phosphatase; ALT = alanine aminotransferase; aPTT = activated partial 
thromboplastin time; AST = aspartate aminotransferase; BUN = blood urea nitrogen; CBC = complete 
blood count; CMP = comprehensive metabolic panel; eGFR = estimated glomerular filtration rate; 
GGT = gamma glutamyltransferase; hCG = human chorionic gonadotropin; MCH = mean corpuscular 
hemoglobin; MCV = mean corpuscular volume; PT = prothrombin time; RBC = red blood cell; T3 = 
triiodothyronine; T4 = thyroxine; TSH = thyroid stimulating hormone; WBC = white blood cell. 


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8.2.3.7. 
Ophthalmologic Examinations 
Ophthalmologic examinations will be performed by a qualified ophthalmologist at Screening 
and Follow-up as indicated in the Schedule of Assessments (Table 1).  Evaluations will 
include visual acuity, pupil exam, confrontation visual field, extraocular motility and 
alignment, interior slit lamp examination, and dilated fundus examination of the retina.  
Additional ophthalmology evaluations may be requested at any other time, if indicated, as 
determined by the investigator. 
8.3. 
Pharmacokinetic Assessments 
Serial, 3-mL blood (plasma) samples will be taken for PK analysis of CPX-POM and 
metabolites at the times and days shown in the Schedule of Assessments (Table 1).  Each PK 
sample should be collected as close as possible to the planned time.  The actual date and time 
of each blood sample collection will be recorded.  PK samples may not be obtained from the 
same site where CPX-POM is infused.  
Urine samples for PK analysis of CPX-POM and metabolites and measurement of urine 
volume will be obtained from each patient in urine collection and storage containers.  
Samples will be collected during Cycle 1 only at the times and days shown in the Study 
Procedures Manual and the Schedule of Assessments (Table 1).  Urine β-glucuronidase 
activity will be determined in the urine samples collected for PK analysis. 
The actual date and time of each sample collection, and the date and time of the previous 
dose of CPX-POM will be recorded.  Processing, storage, and shipping procedures are 
provided in the Study Procedures Manual. 
8.4. 
Pharmacodynamic Assessments 
Serial 7-mL blood samples will be collected to characterize the pharmacologic effects of 
CPX-POM on circulating biomarkers of Wnt and Notch cell signaling pathways at the times 
and days shown in the Schedule of Assessments (Table 1).  Plasma and peripheral blood 
mononuclear cells (PBMCs) will be isolated from blood.  VEGF, IL-6, and IL-8 
concentrations will be measured in plasma by enzyme-linked immunoassay (ELISA).  
Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) will be used to characterize 
gene expression of circulation biomarkers of Wnt and Notch signaling pathways in PBMCs. 
The actual date and time of each sample collection and the date and time of the previous dose 
of CPX-POM will be recorded.  Processing, storage, and shipping procedures are provided in 
the Study Procedures Manual. 


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9. 
STATISTICAL CONSIDERATIONS 
The statistical analysis plan will be developed and finalized before database lock and will 
describe the finalized plans for analysis of study data.  This section is a summary of the 
planned statistical analyses at the time of protocol development. 
9.1. 
Number of Patients 
The maximum anticipated number of patients in the Single Patient and Standard Dose 
Escalation Cohorts will be approximately 24.  In addition to these estimated 24 patients, 
Expansion Cohort(s) may also be enrolled after the MTD is reached.  
The actual number of patients enrolled will depend on the number of dose escalations and the 
need to further characterize individual cohorts.   
9.2. 
Analysis Sets 
9.2.1. 
Safety 
The Safety Set will consist of all patients who receive at least 1 dose of study drug.  All 
safety and PD data will be analyzed using the safety set.  
9.2.2. 
Pharmacokinetics 
The Pharmacokinetic Set will consist of all patients for whom a plasma and/or urine sample 
is obtained and analyzed for determination of plasma drug and metabolites concentration. 
9.3. 
Data Handling Conventions 
9.4. 
Demographic Data and Baseline Characteristics 
Demographic and baseline measurements will be summarized using standard descriptive 
methods. 
9.5. 
Safety Analysis 
Safety data will be presented in by-patient listings.  Categorical safety endpoints will be 
summarized by frequency of events/abnormalities for each dose group and overall.  
Continuous safety endpoints will be summarized using descriptive statistics (n, mean, 
standard deviation, median, Q1, Q3, minimum, maximum) for each dose group and overall. 


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9.5.1. 
Determination of Maximum Tolerated Dose 
The MTD is defined as the highest dose at which 1 or fewer of up to 6 patients experience a 
DLT.  The MTD will be exceeded if 2 or more patients in a cohort of up to 6 patients 
experience a DLT.  The number and proportion of patients who experience a DLT or Grade 2 
or higher AE will be listed and summarized by dose group.  A logistic regression will be used 
to estimate the predicted toxicity probability at each dose level.  Details will be provided in 
the statistical analysis plan.   
9.5.2. 
Extent of Exposure 
Patients’ extent of plasma and urine exposure to CPX-POM and metabolites will be 
summarized by dose group.   
9.5.3. 
Adverse Events 
Clinical and laboratory AEs will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA). System Organ Class (SOC), High-Level Group Term (HLGT), High-
Level Term (HLT), Preferred Term, and Lower-Level Term (LLT) will be attached to the 
clinical database. 
AEs will be summarized on the basis of the date of onset for the event.  A treatment-
emergent AE will be defined as any AE that begins on or after the date of first dose of CPX-
POM.  
Summaries (number and percentage of patients) of treatment-emergent AEs (by SOC, and 
Preferred Term) will be provided by dose group and overall: 
9.5.4. 
Laboratory Evaluations 
Summaries of clinical laboratory data will be provided using descriptive statistics.  No 
inferential statistics will be provided.  Quantitative values and change from baseline in 
quantitative values will be summarized by dose group.  Listings of all laboratory results and 
reference ranges will be provided.   
Graded laboratory abnormalities will be defined using the grading scheme based on CTCAE 
(4.03).  The incidence of treatment-emergent laboratory abnormalities, defined as values that 
increase at least one toxicity grade from baseline at any time post baseline up to and 
including the date of last dose of study drug, will be summarized by treatment group.  If 
baseline data are missing, then any graded abnormality (i.e., at least a Grade 1) will be 
considered treatment emergent. 


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9.5.5. 
Other Safety Evaluations 
Physical examination, ECG (including Holter Monitor), ophthalmologic examination, and 
vital signs data will be summarized by dose group and overall.  Concomitant medications 
will be coded using the World Health Organization Drug Dictionary and listed by dose 
group.   
9.6. 
Pharmacokinetic Analysis 
9.6.1. 
Pharmacokinetics in Plasma 
Plasma concentrations of CPX-POM and its metabolites will be determined by GLP-
validated liquid chromatography tandem mass spectroscopy(LC-MS/MS) assays.  Analysis 
of resultant plasma CPX-POM (and its metabolites) concentration-time data will be 
performed using non-parametric PK data analysis methods using Phoenix WinNonlin 7.0 
(Certara LP, Princeton, NJ).  PK parameters will be listed and summarized for each analyte 
using descriptive statistics (e.g., sample size, arithmetic mean, % coefficient of variation, 
standard deviation, median, minimum, and maximum).  The following PK parameters will be 
determined:   
• Cmax - Maximum observed plasma concentration (Cmax) observed following 
administration of a single dose on Day 1 
• Tmax - Time to reach maximum observed plasma concentration (Cmax) 
• AUC[0-t] - Area under the concentration-time curve following administration of a single 
dose on Day 1 
• AUC[t-∞] - Area under the concentration-time curve following administration of a single 
dose on Day 1 from the last quantifiable concentration (t) to infinity.  
• AUCinf - Area under the curve from time zero to extrapolated infinite time [AUC(0-∞)] 
following administration of a single dose on Day 1 as the sum of AUC[0-t] + AUC(t-∞) 
• Cssmax- Maximum observed plasma concentration at steady-state on Day 5 
• Tssmax - Time to reach maximum observed plasma concentration (Cssmax) on Day 5 
• AUCSS - Area under the concentration-time curve over the dosing interval at steady-state 
following drug administration on Day 5 
• λ - Apparent first-order elimination rate constant 
• t½ - Apparent elimination half-life 
• Cls – Systemic clearance following administration of a single dose on Day 1 
• Clss – Systemic clearance at steady-state 
• Vd – Apparent volume of distribution 
• Vss – Steady-state volume of distribution 


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• Cmax Derived Accumulation Ratio - Cssmax/Cmax 
• AUC Derived Accumulation Ratio - AUCss/AUC(0 - ∞) 
• CLr – Single dose (Day 1) and steady-state (Day 5) renal clearance  
Plasma drug and metabolite concentration-time data and derived plasma PK parameters will 
be presented in tabular and graphic format.  
9.6.2. 
Pharmacokinetics in Urine 
Urine concentrations of CPX-POM and its metabolites will be determined by GLP-validated 
LC-MS/MS assays.  Urine PK parameters will be generated using non-parametric PK data 
analysis methods, listed, and summarized for each analyte using descriptive statistics (e.g., 
sample size, arithmetic mean, % coefficient of variation, standard deviation, median, 
minimum, and maximum).  The following PK parameters will be determined:   
• Mass excreted 
• Excretion rate 
• Cumulative mass excreted 
Urine β–glucuronidase activity will be measured for each patient and summarized.  
9.6.3. 
Covariates and Pharmacokinetics 
The influence of dose, single versus multiple dose administration, β-glucuronidase activity, 
and other potential covariates (e.g., creatinine clearance, concomitant medications, 
concurrent disease) on CPX-POM and metabolite exposure will be examined in an 
exploratory fashion given the limited sample size. 
9.7. 
Pharmacodynamic Analyses 
The pharmacologic effects of CPX-POM on circulating Wnt and Notch cell signaling 
biomarkers will be characterized.  Plasma concentrations of VEGF, IL-6, and IL-8 will be 
determined prior to, during, and following CPX-POM treatment for each cycle by ELISA.  
Expression of survivin; Notch receptors 1, 2, and 3; Notch ligand Jagged-1, Notch target 
proteins HES1, Hey1, cyclin D1, and cMyc; as well as ϒ-Secretase proteins Presinilin-1 and 
Nicastrin, will be determined in PBMCs by qRT-PCR.   
Relationships between observed biomarker changes and drug and/or metabolite exposure as 
well as other measures will be explored using descriptive statistics, and/or additional PK/PD 
modeling to support the dose selection for future studies.  Demographic and baseline 
characteristics may be included in the modeling analysis. 


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9.8. 
Interim Analyses 
No formal interim analysis is planned.  After each cohort is completed, an SRC comprised of 
the CRO Medical Monitor, Principal Investigator(s), and  Sponsor representatives will meet 
to discuss the data and decide upon the next dose escalation.  In addition, after completion of 
Cycle 1 for the first 4 to 6 patients, the SRC will review safety, PK, and PD data to determine 
if any changes to the dosing schedule are indicated. 


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10. 
REGULATORY, ETHICAL, AND STUDY OVERSIGHT 
CONSIDERATIONS 
10.1. 
Regulatory and Ethical Considerations 
10.1.1. 
Institutional Review Board/Ethics Committee 
IRBs must be constituted according to the applicable state and federal requirements of each 
participating location including International Council on Harmonisation (ICH) Good Clinical 
Practice (GCP). 
It is the responsibility of each investigational site to submit the protocol, IB, patient ICF, 
patient recruitment materials (if applicable), and other documentation as required by the IRB 
to their IRB for review and approval.  A copy of the written approval must be provided to the 
sponsor or CRO.  The documentation should clearly mention the approval/favorable opinion 
of the protocol, the patient ICF, and patient recruitment materials (if applicable), including 
respective version dates.  The written approval and a list of the voting members, their titles or 
occupations, and their institutional affiliations must be obtained from the IRB(s) and 
provided to the sponsor or CRO prior to the release of clinical study supplies to the 
investigational site and commencement of the study.  If any member of the IRB has direct 
participation in this trial, written notification regarding his or her abstinence from voting 
must also be obtained. 
Sites must adhere to all requirements stipulated by their respective IRB.  This includes 
notification to the IRB regarding: protocol amendments, updates to the patient informed 
consent, recruitment materials intended for viewing by patients, IND safety reports, serious 
and unexpected AEs, reports and updates regarding the ongoing review of the trial at 
intervals specified by the respective IRB, and submission of final study reports and 
summaries to IRB. 
It is the responsibility of each investigational site to submit information to the appropriate 
IRB for annual review and annual re-approval. 
10.1.2. 
Ethical Conduct of the Study 
This study will be conducted according to the protocol, Code of Federal Regulations (21 
CFR Parts 50, 54, 56, and 312), the Declaration of Helsinki, and ICH GCP.  Each 
investigator will conduct the trial according to applicable local or regional regulatory 
requirements. 


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10.1.3. 
Informed Consent 
Prior to any study procedures being performed, patients and the person conducting the 
consent discussion will be required to sign and date the IRB-approved ICF, and each patient 
will be given a copy.  In addition, this information should be recorded in the patient’s 
medical record (i.e., source document). 
The written consent document will embody the elements of informed consent as described in 
the Declaration of Helsinki, the Code of Federal Regulations (21 CFR Part 50.25), the ICH 
GCP guidelines, and in accordance with any local regulations.  The investigator is 
responsible for the preparation, content, and IRB approval of the informed consent.  The ICF 
must be approved by the site-designated IRB and be acceptable to the sponsor or CRO. 
The ICF must be written in a language fully comprehensible to the prospective patient.  The 
investigator or designee shall give the patient adequate opportunity to read the ICF before it 
is signed and dated.  Information should be given in both oral and written form whenever 
possible and in the manner deemed appropriate by the IRB.  Patients must be given ample 
opportunity to inquire about details of the study. 
10.1.4. 
Confidentiality 
The investigator must assure that patients’ anonymity will be strictly maintained and that 
their identities are protected from unauthorized parties.  
Patients will be assigned a unique identifier by the sponsor.  Any patient records or datasets 
that are transferred to the sponsor will contain the identifier only; patient names or any 
information which would make the patient identifiable will not be transferred.  
NOTE:  The investigator must keep a screening log showing codes, names, and addresses for 
all patients screened and for all patients enrolled in the trial. 
The patient must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law.  The level of disclosure must also be 
explained to the patient.  
The patient must be informed that his/her medical records may be examined by clinical 
quality assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB members, and by inspectors from regulatory authorities. 
The investigator agrees that all information received from CicloMed, including but not 
limited to the Investigator Brochure, this protocol, CRFs, the investigational new drug, and 
any other study information, remain the sole and exclusive property of CicloMed during the 
conduct of the study and thereafter.  This information is not to be disclosed to any third party 
(except employees or agents directly involved in the conduct of the study or as required by 


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law) without prior written consent from CicloMed.  The investigator further agrees to take all 
reasonable precautions to prevent the disclosure by any employee or agent of the study site to 
any third party or otherwise into the public domain. 
10.2. 
Study Oversight 
10.2.1. 
Data Quality Assurance 
All patient data relating to the study will be recorded in a printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (e.g., laboratory data).  The investigator 
is responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.  
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.  
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents.  
The sponsor or designee is responsible for the data management of this study including 
quality checking of the data.  
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of patients are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.  
10.2.2. 
Source Documents 
Source documents provide evidence for the existence of the patient and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site. 
Data reported on the CRF that are transcribed from source documents must be consistent 
with the source documents or the discrepancies must be explained.  The investigator may 
need to request previous medical records or transfer records, depending on the study. Also, 
current medical records must be available. 
Definitions of what constitutes source data can be found in the Study Procedures Manual. 
10.2.3. 
Study and Site Closure 
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed on a 


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rolling basis upon database lock for each site individually or as the Sponsor determines.  A 
study site is considered closed when all required documents, study supplies, and 
investigational product have been collected and/or destroyed, and a study-site closure visit 
has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but 
are not limited to: 
• Failure of the investigator to comply with the protocol, the requirements of the IRB or 
local health authorities, the sponsor's procedures, or GCP guidelines 
• Inadequate recruitment of patients by the investigator 
• Discontinuation of further CPX-POM development 
10.2.4. 
Reporting of Results and Publications 
CicloMed will fulfill its commitment to publicly disclose the results of this study through 
posting the results on the www.clinicaltrials.gov web site.   
A clinical study report will be prepared and provided to the regulatory agency(ies).  
CicloMed will ensure that the report meets the standards set out in the ICH Guideline for 
Structure and Content of Clinical Study Reports (ICH E3). Note that an abbreviated report 
may be prepared in certain cases. 
Any investigator will submit any proposed publication or presentation along with the 
respective scientific journal or presentation forum at least 30 days before submission of the 
publication or presentation. The investigator will comply with CicloMed’s request to delete 
references to its confidential information (other than the study results) in any paper or 
presentation and agrees to withhold publication or presentation for an additional 60 days in 
order to obtain patent protection if deemed necessary. 
The results of this study may be published or presented at scientific meetings.  If this is 
foreseen, the investigator agrees to submit all manuscripts or abstracts to the sponsor before 
submission. This allows the sponsor to protect proprietary information and to provide 
comments.  
The sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the sponsor will generally support 
publication of multicenter studies only in their entirety and not as individual site data. In this 
case, a coordinating investigator will be designated by mutual agreement. 


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Authorship will be determined by mutual agreement and in line with International Committee 
of Medical Journal Editors authorship requirements. 
10.2.5. 
Study Files and Retention of Records 
The investigator must maintain adequate and accurate records to enable the conduct of the 
study to be fully documented and the study data to be subsequently verified. These 
documents should be classified into at least the following two categories: (1) investigator’s 
study file, and (2) patient clinical source documents. 
The investigator’s study file will contain the protocol/amendments, CRF and query forms, 
IRB, and governmental approval with correspondence, informed consent, drug records, staff 
curriculum vitae and authorization forms, and other appropriate documents and 
correspondence. 
The required source data includes at least the following information for each patient: 
• patient identification (name, date of birth, gender); 
• documentation that patient meets eligibility criteria, i.e., history, physical examination, 
and confirmation of diagnosis (to support inclusion and exclusion criteria); 
• participation in trial (including trial number); 
• trial discussed and date of informed consent; 
• dates of all visits; 
• documentation that protocol specific procedures were performed; 
• results of efficacy parameters, as required by the protocol; 
• start and end date (including dose regimen) of trial medication; 
• record of all AEs and other safety parameters (start and end date, and preferably 
including causality and intensity); 
• concomitant medication (including start and end date, dose if relevant; dose changes 
should be motivated); 
• date of trial completion and reason for early discontinuation, if applicable. 
All clinical study documents must be retained by the investigator until at least 2 years after 
the last approval of a marketing application in an ICH region (i.e., United States, Europe, or 
Japan) and until there are no pending or contemplated marketing applications in an ICH 
region; or, if no application is filed or if the application is not approved for such indication, 
until 2 years after the investigation is discontinued and regulatory authorities have been 
notified. Investigators may be required to retain documents longer if required by applicable 
regulatory requirements, by local regulations, or by an agreement with CicloMed. The 
investigator must notify CicloMed before destroying any clinical study records. 


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Should the investigator wish to assign the study records to another party or move them to 
another location, CicloMed must be notified in advance (i.e. in the case of a Principal 
Investigator moving to a new location, retiring, etc.).  If a study site is assigned to another 
investigator for archival oversight or if the files are to be moved, this change will be noted in 
a memo, the Sponsor will be contacted, and the IRB will be notified depending on the IRB 
requirements. 
If the investigator cannot guarantee this archiving requirement at the study site for any or all 
of the documents, special arrangements must be made between the investigator and 
CicloMed to store these in sealed containers outside of the site so that they can be returned 
sealed to the investigator in case of a regulatory audit.  When source documents are required 
for the continued care of the patient, appropriate copies should be made for storage outside of 
the site. 
Biological samples at the conclusion of this study may be retained in storage by the sponsor 
for a period up to 2 years for purposes of this study. 
10.2.6. 
Case Report Forms 
For each patient enrolled, a CRF must be completed and signed by the Principal Investigator 
or sub-investigator (as appropriate) within a reasonable time period after data collection.  
This also applies to records for those patients who fail to complete the study (even during a 
screening period if a CRF was initiated).  If a patient withdraws from the study, the reason 
must be noted on the CRF.  If a patient is withdrawn from the study because of a treatment-
limiting AE, thorough efforts should be made to clearly document the outcome. 
10.2.7. 
Inspections 
The investigator should understand that source documents for this trial should be made 
available to appropriately qualified personnel from CicloMed or its representatives, to IRBs, 
or to regulatory authority or health authority inspectors. 
10.2.8. 
Protocol Compliance 
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol. 
10.2.9. 
Study Discontinuation 
Both the sponsor and the investigator reserve the right to terminate the study at any time. 
Should this be necessary, both parties will arrange discontinuation procedures and notify the 
appropriate regulatory authority(ies) and IRBs.  In terminating the study, CicloMed and the 
investigator will assure that adequate consideration is given to the protection of the patients’ 
interests. 


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11. 
REFERENCES 
Abrams BB, Hanel H. Hoehler T. Ciclopirox olamine: a hydroxypyridone antifungal agent. 
Clin Dermatol. 1991;9(4):471-477. 
Bohn M, Kraemer KT. Dermatopharmacology of ciclopirox nail lacquer topical solution 8% 
in the treatment of onychomyosis. J Am Acad Dermatol. 2000;43(4):S57-S69. 
Clement PMJ, Hanauske-Abel HM, Wolff EC, Kleinman HK, Park MH. The antifungal drug 
ciclopirox inhibits deoxyhpusine and proline hydroxylation, endothelial cell growth and 
angiogenesis in vitro. Int J Cancer. 2002;100:491-498.  
ClinicalTrials.gov web site. Available at: https://clinicaltrials.gov/. Accessed May 18, 2017.  
CPX-POM Investigator’s Brochure. CicloMed LLC. 2017. 
Dihazi H, Dihazi GH, Jahn O, Meyer S, Nolte J, Asif AR, Mueller GA, Engel W. 
Multipotent adult germline stem cells and embryonic stem cells functional proteomics 
revealed an important role of eukaryotic initiation factor 5A (Eif5a) in stem cell 
differentiation. J Proteome Res. 2011;10:1962-1973. 
Eberhard Y, McDermott SP, Wang X, Gronda M, Venugopal A, Wood TE, Hurren R, Datti 
A, Batey RA, Wrana J, Antholine WE, Dick JE, Schimmer AD. Chelation of intracellular 
iron with the antifungal agent ciclopirox olamine induces cell death in leukemia and 
myeloma cells. Blood. 2009;114(14):3064-3073. 
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck 
S, Gwyther S, Mooney M, Rubinstein L, Shakar L, Dodd L, Kaplan R, Lacombe D, Verweij 
J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). 
Eur J Cancer. 2009;45:228-247.  
[FDA] Food and Drug Administration. Guidance for Industry – S9 Nonclinical Evaluation 
for Anticancer Pharmaceuticals. March 2010. Available at: 
https://www.fda.gov/downloads/Drugs/Guidances/ucm085389.pdf. Accessed September 18, 
2017.  
Gupta AK. Ciclopirox: an overview. Int J Dermatol. 2001;40(5):305-310. 
Gupta AK, Plott T. Ciclopirox: a broad-spectrum antifungal with antibacterial and anti-
inflammatory properties. Int J Dermatol. 2004; 43(Suppl 1):3-8.  
Gupta AK, Sauder DN, Shear NH. Antifungal agents: an overview. Part 1. J Am Acad 
Dermatol. 1994;30(5 Pt 1):677-698. 
Hanel H, Smith-Kurtz E, Pastowsky S. Therapy of seborrheic eczema with an antifungal 
agent with an antiphlogistic effect. Mycoses. 1991;34(Suppl 1):91-93. 


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Kellner HM, Arnold C, Christ OE, Eckert HG, Herok J, Hornke I, Rupp W. Investigations on 
the pharmacokinetics and biotransformation of the antimycotic ciclopiroxolamine in animals 
and humans after topical and systemic application. Anzneim-Forsch/Drug Res. 1981; 31(II). 
No. 8a:1337-1353.  
Kwong W-L, Lok C-N, Tse C-W, Wong E L-M, Che C-M. Anti-cancer iron(ii) complexes of 
pentadentate n-donor ligands: cytotoxicity, transcriptomics analyses, and mechanisms of 
action. Chem Eur J. 2015;21:3062–3072. 
Le Tourneau C, Lee JJ, Siu LL. Dose escalation methods in phase 1 cancer clinical trials. 
JNCI. 2009;101(10):708-720.  
Minden MD, Hogge DE, Weir SJ, Kasper J, Webster DA, Patton L, Jitkova Y, Hurren R, 
Gronda M, Goard CA, Rajewski LG, Haslam JL, Heppert KE, Schorno K, Chang H, 
Brandwein JM, Gupta V, Schuh AC, Trudel S, Yee KW, Reed GA, Schimmer AD. Oral 
ciclopirox olamine displays biological activity in a phase 1 study in patients with advanced 
hematologic malignancies. Am J Hematol. 2014; 89(4):363-368.  
Oken M, Creech R, Tormey D, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity 
and response criteria of the Eastern Cooperative Oncology Group. Am J Clin 
Oncol. 1982;5:649-655. 
Sakurai K, Sakeguchi T, Yamaguchi H, Iwata K. Mode of action of 6-cyclohexyl-1-hydroxy-
4-methyl-2(1H)-pyridone ethanolamine salt (Hoe296). Chemotherapy.1978;24(2):68-76. 
Sidarovich V, Adami V, Gatto P, Greco V, Tebaldi T, Tonini GP, Quattrone A. Translational 
downregulation of hsp90 expression by iron chelators in neuroblastoma cells. Mol 
Pharmacol. 2015;87(3):513-524. 
Song S, Christova T, Perusini S, Alizadeh S, Bao RY, Miller BW, Hurren R, Jitkova Y, 
Gronda M, Isaac M, Joseph B, Subramanian R, Aman A, Chan A, Hogge DE, Weir SJ, 
Kaspar J, Schimmer AD, Al-awar R, Wrana JL, Altisano L. WNT inhibitor screen reveals 
iron dependence of β-catenin signaling in cancers. Cancer Res. 2011;71:7628-7639.  
Szüts D, Krude T. Cell cycle arrest at the initiation step of human chromosomal DNA 
replication causes DNA damage. J Cell Sci. 2004;117(Pt 21):4897-4908.  


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12. 
APPENDIX 
Appendix 1. 
RECIST Criteria Guidance 
Time Point Response of Measurable Disease (Target Lesions) with or without  
Non-Measurable Disease (Non-Target Lesions) 
Target Lesion Response 
Non-Target 
Lesion Response 
New Lesions 
Overall Response 
CR 
CR 
No 
CR 
CR 
Non-CR/Non-PD 
No 
PR 
CR 
NE 
No 
PR 
PR 
Non-PD or NE 
No 
PR 
SD 
Non-PD or NE 
No 
SD 
NE 
Non-PD 
No 
NE 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
Abbreviations:  CR = Complete Response, PR = Partial Response, SD = Stable Disease, PD = Progressive 
Disease, and NE = Not All Evaluated 
 
 
Time Point Response of Non-Measurable Disease Only (Non-Target Lesions) 
Non-Target Lesion Response 
New Lesions 
Overall Response 
CR 
No 
CR 
Non-CR/Non-PD 
No 
Non-CR/Con-PD 
NE 
No 
NE 
Unequivocal Progression 
Yes or No 
PD 
Any 
Yes 
PD 
Abbreviations:  CR = Complete Response, PD = Progressive Disease, NE = Not All Evaluated 
Note:  Non-CR/Non-PD is preferred over “Stable Disease” for non-target disease since SD is increasingly 
used as endpoint for assessment of efficacy in some trials, so to assign this category when no lesions can be 
measured is not advised 
 
Note:  If a CR is truly met at a time point, then any disease seen at a subsequent time point, even disease 
meeting PR criteria relative to baseline, makes the disease PD at that time point since disease must have 
reappeared after CR. 
 
Source:  Eisenhauer et al, 2009 
 

SAP_001.pdf: 
 
 
 
 
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SPONSOR: 
 
CicloMed 
 
PROTOCOL NUMBER: 
 
 
CPX-POM-001 
 
 
 
STATISTICAL ANALYSIS PLAN 
(TFL shells) 
 
Author: 
Jean-Luc Beffy 
Version: 
Version 1.0 
Date: 
02FEB2018 
 
 
 


 
 
 
 
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Cover and signature pages 
 
Sponsor: 
CicloMed 
Protocol Number: 
CPX-POM-001 
Study Title: 
A Phase 1, First-in-Human, Safety, Dose Tolerance, Pharmacokinetics, 
and Pharmacodynamics Study of CPX-POM in Patients with Advanced 
Solid Tumors 
Document Version No 
Version 1.0 
 
We, the undersigned, confirm that we have read, understood and agree to the content of this document 
and hereby authorise its approval. 
 
Name 
Title, Organisation 
Signature 
Date 
Jean-Luc Beffy 
Principal Biostatistician  
Cmed CRS Ltd 
 
 
Tony Cornelius 
Senior Manager Biostatistics 
Cmed CRS Ltd 
 
 
Scott Weir, Pharm. D, Ph. D. 
Chief Scientific Officer 
CicloMed 
 
 
Dr. Bill McCulloch 
Medical Advisor 
CicloMed 
 
 
 
 
 


 
 
 
 
 
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Table of Contents 
COVER AND SIGNATURE PAGES ........................................................................................................................................................................................................................2 
Table 14.1-1 – Patients disposition (All patients) ..............................................................................................................................................................................................9 
Table 14.1-2 – Number (%) of Patients in the Analysis Populations (All patients) ..........................................................................................................................................12 
Table 14.1-3 – Summary of Demography (ITT Population) .............................................................................................................................................................................13 
Table 14.1-4 – Protocol Deviations (Safety Population)..................................................................................................................................................................................18 
Table 14.1-5.1 – Disease Characteristics (Safety Population) .........................................................................................................................................................................19 
Table 14.1-5.2 – Other Medical History (Safety Population) ...........................................................................................................................................................................21 
Table 14.1-6.1.1 – Prior Medications by Therapeutic Class and Preferred Term (Safety Population) .............................................................................................................23 
Table 14.1-6.1.2 – Concomitant Medications by Therapeutic Class and Preferred Term (Safety Population) ................................................................................................24 
Table 14.1-7 – Overall Exposure to Study Drug and Drug Compliance (Safety Population) ............................................................................................................................25 
Table 14.2.1 – Patients who have had at least one other post-baseline tumor assessment (Efficacy Population) .........................................................................................26 
Table 14.2.2 – Summary of Patients Responses (Efficacy Population) ............................................................................................................................................................27 
Table 14.3-1.1 – Overview of Adverse Events (Safety Population) .................................................................................................................................................................29 


 
 
 
 
 
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Table 14.3-1.2 – Number (%) of Patients with Treatment-Emergent Adverse Events by System Organ Class and Preferred Term (Safety Population) ................................30 
Table 14.3-1.3 – Number (%) of Patients with Related Treatment-Emergent Adverse Events by System Organ Class and Preferred Term (Safety Population) ...................31 
Table 14.3-1.4 – Number (%) of Patients with Serious Treatment-Emergent Adverse Events by System Organ Class and Preferred Term (Safety Population) ...................31 
Table 14.3-1.5 – Number (%) of Patients with Serious Related Treatment-Emergent Adverse Events by System Organ Class and Preferred Term (Safety Population) ......31 
Table 14.3-1.6 – Number (%) of Patients with Treatment-Emergent Adverse Events Leading to Discontinuation by System Organ Class and Preferred Term (Safety 
Population) .....................................................................................................................................................................................................................................................31 
Table 14.3-1.7 – Number (%) of Patients with Treatment-Emergent Adverse Events by System Organ Class, Preferred Term and Maximal Severity (Safety Population) ..32 
Table 14.3-1.8 – Number (%) of Patients with Related Treatment-Emergent Adverse Events by System Organ Class, Preferred Term and Maximum Severity (Safety 
Population) .....................................................................................................................................................................................................................................................33 
Table 14.3-1.9 – Number (%) of Patients with Treatment-Emergent Adverse Events of Special Interest by System Organ Class and Preferred Term (Safety Population) ..34 
Table 14.3-2.1.1 – Summary of Hematology Laboratory Data  (Safety Population) ........................................................................................................................................35 
Table 14.3-2.1.2 – Outside of Normal Range - Shift Table for Hematology Laboratory Parameters (Safety Population) ...............................................................................36 
Table 14.3-2.1.3 – Clinician Assessment - Shift Table for Hematology Laboratory Parameters (Safety Population) ......................................................................................38 
Table 14.3-2.1.4 – On-study Hematology Adverse Events: Worst NCI-CTCAE Grade per patient (Safety Population) ....................................................................................39 
Table 14.3-2.1.5 – Shift table of Worst NCI-CTCAE Grade for Hematological parameters (Safety Population)...............................................................................................41 


 
 
 
 
 
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Table 14.3-2.2.1 – Summary of Clinical Chemistry Laboratory Data  (Safety Population) ...............................................................................................................................42 
Table 14.3-2.2.2 – Outside of Normal Range - Shift Table for Clinical Chemistry Laboratory Parameters (Safety Population) ......................................................................42 
Table 14.3-2.2.3 – Clinician Assessment - Shift Table for Clinical Chemistry Laboratory Parameters (Safety Population) .............................................................................42 
Table 14.3-2.2.4 – On-study Clinical Chemistry Adverse Events: Worst NCI-CTCAE Grade per patient (Safety Population) ...........................................................................42 
Table 14.3-2.2.5 – Shift table of Worst NCI-CTCAE Grade for Clinical Chemistry Laboratory parameters (Safety Population) .......................................................................43 
Table 14.3-2.3.1 – Summary of Coagulation Laboratory Data  (Safety Population) ........................................................................................................................................43 
Table 14.3-2.4 – Summary of Thyroid Panel Laboratory Data  (Safety Population) ........................................................................................................................................43 
Table 14.3-2.5.1 – Summary of Urinalysis Laboratory Data  (Safety Population) ...........................................................................................................................................44 
Table 14.3-2.5.2 – Outside of Normal Range - Shift Table for Urinalysis Laboratory Parameters (Safety Population) ...................................................................................44 
Table 14.3-2.5.3 – Clinician Assessment - Shift Table for Urinalysis Laboratory Parameters (Safety Population) ..........................................................................................44 
Table 14.3-2.5.4 – On-study Urinalysis Adverse Events: Worst NCI-CTCAE Grade per patient (Safety Population) ........................................................................................44 
Table 14.3-2.5.5 – Shift table of Worst NCI-CTCAE Grade for Urinalysis Laboratory parameters (Safety Population) ....................................................................................45 
Table 14.3-2.6 – Summary of Other Laboratory Data  (Safety Population) .....................................................................................................................................................46 
Table 14.3-3.1 – Summary of Vital Signs  (Safety Population) ........................................................................................................................................................................47 


 
 
 
 
 
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Table 14.3-3.2 – Summary of Abnormal Vital Signs (Safety Population).........................................................................................................................................................48 
Table 14.3-4.1 – Summary of ECG Parameters (Safety Population) ................................................................................................................................................................51 
Table 14.3-4.2 – Summary of Abnormal ECG Intervals (Safety Population) ....................................................................................................................................................52 
Listing 16.1.7-1 – Treatment Administration  (All Patients) ............................................................................................................................................................................54 
Listing 16.1.7-2 – Infusion Interruption  (All Patients) ....................................................................................................................................................................................55 
Listing 16.2.1-1.1 – Preface to Inclusion and Exclusion Criteria ......................................................................................................................................................................56 
Listing 16.2.1-1.2 – List of Failed Inclusion and Exclusion Criteria (All Patients) .............................................................................................................................................57 
Listing 16.2.1-2 – Patient Disposition (All Patients) ........................................................................................................................................................................................58 
Listing 16.2.2 – Protocol Deviations (All Patients) ..........................................................................................................................................................................................59 
Listing 16.2.3-1 – Demographic and Baseline Characteristics (All Patients) ....................................................................................................................................................60 
Listing 16.2.3-2 – HIV, Hepatitis and Pregnancy Test Results (All Patients) ....................................................................................................................................................61 
Listing 16.2.4-1 – Cancer History (All Patients) ...............................................................................................................................................................................................63 
Listing 16.2.4-2 – Prior Cancer Therapies (All Patients)...................................................................................................................................................................................64 
Listing 16.2.4-3 – Other Medical History (All Patients) ...................................................................................................................................................................................65 


 
 
 
 
 
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Listing 16.2.4-4 – Cardiac Function (All Patients) ............................................................................................................................................................................................66 
Listing 16.2.4-5 – Ophthalmologic Exam (All Patients)....................................................................................................................................................................................67 
Listing 16.2.4-6 – RECIST Target Lesions (All Patients) ....................................................................................................................................................................................68 
Listing 16.2.4-7 – RECIST Non-Target Lesions (All Patients) ............................................................................................................................................................................69 
Listing 16.2.4-8 – Prior and Concomitant Medications (All Patients) ..............................................................................................................................................................70 
Listing 16.2.5 – Drug Exposure (All Patients)...................................................................................................................................................................................................71 
Listing 16.2.6-1 – Urine concentrations of CPX-POM and Metabolites (All Patients)......................................................................................................................................72 
Listing 16.2.6-2 – Plasma concentrations of CPX-POM and Metabolites (All Patients) ...................................................................................................................................72 
Listing 16.2.6-3 – Plasma concentrations of Biomarkers Assays (All Patients) ................................................................................................................................................73 
Listing 16.2.6-4 – PBMC Biomarkers Assays (All Patients) ..............................................................................................................................................................................73 
Listing 16.2.6-5 – Urine beta-glucuronidase activity (All Patients)..................................................................................................................................................................74 
Listing 16.2.7-1 – Adverse Events (All Patients) ..............................................................................................................................................................................................75 
Listing 16.2.7-2 – Serious Adverse Events (All Patients) ..................................................................................................................................................................................76 
Listing 16.2.7-3 – Adverse Events Leading to Discontinuation (All Patients) ..................................................................................................................................................76 


 
 
 
 
 
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Listing 16.2.7-4 – Adverse Events Leading to Death (All Patients) ..................................................................................................................................................................76 
Listing 16.2.8-1 – Patients Laboratory Profile: Hematology (All Patients) ......................................................................................................................................................77 
Listing 16.2.8-2 – Patients Laboratory Profile: Clinical Chemistry (All Patients) .............................................................................................................................................78 
Listing 16.2.8-3 – Patients Laboratory Profile: Coagulation and Thyroid Panel (All Patients) .........................................................................................................................78 
Listing 16.2.8-4 – Patients Laboratory Profile: Urinalysis (All Patients) ..........................................................................................................................................................78 
Listing 16.2.8-5 – Vital Signs (All Patients) ......................................................................................................................................................................................................79 
Listing 16.2.8-6 – ECG Results and Interpretation (All Patients) .....................................................................................................................................................................80 
 
 
 


 
 
 
 
 
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Protocol: CPX-POM-001 
               --- DELIVERY TYPE ---- 
 
Table 14.1-1 – Patients disposition 
(All patients) 
 
Page 1 of Y 
Cycle 
CPX-POM 
30 mg/m^2 
N=1 
n (%) 
CPX-POM  
[D2] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D3] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D4] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D5] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D6] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D7] mg/m^2 
N=X 
n (%) 
 
Cycle 1 
  Treated 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Completed the cycle [a] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Discontinued from the cycle 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
  Reason for discontinuation from  
  the cycle 
 
 
 
 
 
    Dose Limitimg Toxicity 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Withdrawn Consent 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Physician Decision 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Death 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Lost to Follow-up 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
Percentages are based on the number of patients enrolled. 
[a] A patient completed Cycle 1 if s/he attended visit Day 10 (if Cycle 1 was not the last cycle) or Visit Day 22 (if Cycle 1 was 
the last cycle). 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                          
Filename: (Specify file name.rtf) 
 
 
 
 
 


 
 
 
 
 
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Protocol: CPX-POM-001 
               --- DELIVERY TYPE ---- 
 
Table 14.1-1 – Patients disposition 
(All patients) 
 
Page 2 of Y 
Cycle 
CPX-POM 
30 mg/m^2 
N=1 
n (%) 
CPX-POM  
[D2] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D3] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D4] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D5] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D6] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D7] mg/m^2 
N=X 
n (%) 
 
Cycle 2 
  Treated 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Completed the cycle [b] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Discontinued from the cycle 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
  Reason for discontinuation from  
  the cycle 
 
 
 
 
 
    Dose Limitimg Toxicity 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Withdrawn Consent 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Physician Decision 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Death 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Lost to Follow-up 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
<repeat until last-1 cycle> 
 
 
 
 
 
 
 
 
 
 
 
 
 
Percentages are based on the number of patients enrolled. 
[b] A patient completed Cycle 2 (or any next cycle until last-1 cycle) if s/he attended visit Day 6 (if Cycle 2 or any next cycle 
was not the last cycle) or Visit Day 22 (if Cycle 2 or any next cycle was the last cycle). 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                          
Filename: (Specify file name.rtf) 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 11 of 80 
 
Protocol: CPX-POM-001 
               --- DELIVERY TYPE ---- 
 
Table 14.1-1 – Patients disposition 
(All patients enrolled) 
 
Page X of Y 
Cycle 
CPX-POM 
30 mg/m^2 
N=1 
n (%) 
CPX-POM  
[D2] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D3] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D4] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D5] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D6] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D7] mg/m^2 
N=X 
n (%) 
 
Last Cycle 
  Treated 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Completed the cycle [c] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Discontinued from the cycle 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
  Reason for discontinuation from  
  the cycle 
 
 
 
 
 
    Dose Limitimg Toxicity 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Withdrawn Consent 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Physician Decision 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Death 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Lost to Follow-up 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
  Attended the follow-up visit  
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  (Day 28) 
 
 
 
 
 
 
Percentages are based on the number of patients enrolled. 
[c] A patient completed the Last Cycle if s/he attended visit Day 22. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                          
Filename: (Specify file name.rtf) 
PROGRAMMING NOTES:  
• 
Display all the reasons for discontinuation where there is at least one patient within that category 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 12 of 80 
 
 
Protocol: CPX-POM-001 
               --- DELIVERY TYPE ---- 
 
Page 1 of 1 
 
CPX-POM 
30 mg/m^2 
N=1 
n (%) 
CPX-POM  
[D2] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D3] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D4] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D5] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D6] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D7] mg/m^2 
N=X 
n (%) 
 
 
 
 
 
 
 
 
Safety Population 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Efficacy Population 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
PK Population 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
Percentages are based on the number of enrolled patients. 
The Safety population includes all patients who have received at least one dose of CPX-POM. 
The Efficacy population includes all patients who have received at least one dose of CPX-POM, had RECIST measurable disease at 
baseline and had at least one other post-baseline tumor assessment. 
The PK population includes all patients for whom at least one plasma and/or urine sample has been obtained and analyzed for 
determination of plasma drug and metabolites concentration.  
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                          
Filename: (Specify file name.rtf) 
 
 
PROGRAMMING NOTES:  
• 
For the safety population, patients are displayed based on the actually received treatment. 
 
 
 
Table 14.1-2 – Number (%) of Patients in the Analysis Populations 
(All patients) 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 13 of 80 
 
 
CPX-POM 
30 mg/m^2 
N=1 
CPX-POM  
[D2] mg/m^2 
N=X 
CPX-POM  
[D3] mg/m^2 
N=X 
CPX-POM  
[D4] mg/m^2 
N=X 
CPX-POM  
[D5] mg/m^2 
N=X 
CPX-POM  
[D6] mg/m^2 
N=X 
CPX-POM  
[D7] mg/m^2 
N=X 
Protocol: CPX-POM-001 
               --- DELIVERY TYPE ---- 
 
Page 1 of 3 
Table 14.1-3 – Summary of Demography 
(ITT Population) 
 
Age [a] (years)  
  n  
XX 
XX 
XX 
XX 
XX 
XX 
XX 
  Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
  Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
  Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Age group [n (%)] 
 
  < 65 years 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  ≥ 65 years 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Sex [n (%)] 
  Male 
XX (XX.X) XX (XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
  Female 
XX (XX.X) XX (XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
 
 
 
 
 
 
Race [n (%)] 
  White 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Black or African American 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Asian 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  American Indian or Alaska Native 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Native Hawaiian or 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Other Pacific Islander 
 
 
 
 
 
 
  Other 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
[a] Age at Screening.  
[b] Body mass index (BMI) (kg/m²) = Weight (kg) / (Height (m))^2. 
[c] The denominator is the number of females in each dose group. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                        
Filename: (Specify file name.rtf) 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 14 of 80 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 15 of 80 
 
 
CPX-POM 
30 mg/m^2 
N=1 
CPX-POM  
[D2] mg/m^2 
N=X 
CPX-POM  
[D3] mg/m^2 
N=X 
CPX-POM  
[D4] mg/m^2 
N=X 
CPX-POM  
[D5] mg/m^2 
N=X 
CPX-POM  
[D6] mg/m^2 
N=X 
CPX-POM  
[D7] mg/m^2 
N=X 
 
 
 
Protocol: CPX-POM-001 
                --- DELIVERY TYPE ---- 
 
Page 2 of 3 
Table 14.1-3 – Summary of Demography 
(ITT Population) 
 
 
 
 
 
  
 
Female of child bearing potential  
[n (%)] [c] 
  Yes 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
  No 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
 
Country [n (%)] 
  XXXXX 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
  XXXXX 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
  XXXXX 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
 
Height (cm) 
  n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
  Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
  Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
  Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
  
 
 
 
[a] Age at Screening.  
[b] Body mass index (BMI) (kg/m²) = Weight (kg) / (Height (m))**2. 
[c] The denominator is the number of females in each dose group. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                       
Filename: (Specify file name.rtf) 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 16 of 80 
 
 
CPX-POM 
30 mg/m^2 
N=1 
CPX-POM  
[D2] mg/m^2 
N=X 
CPX-POM  
[D3] mg/m^2 
N=X 
CPX-POM  
[D4] mg/m^2 
N=X 
CPX-POM  
[D5] mg/m^2 
N=X 
CPX-POM  
[D6] mg/m^2 
N=X 
CPX-POM  
[D7] mg/m^2 
N=X 
Protocol: CPX-POM-001 
                --- DELIVERY TYPE ---- 
 
Page 3 of 3 
Table 14.1-3 – Summary of Demography 
(ITT Population) 
 
 
 
 
 
  
 
Weight (kg) 
  n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
  Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
  Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
  Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
BMI [b] (kg/m^2) 
  n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
  Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
  Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
  Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
BSA [d] (kgxm) 
 
 
 
 
 
 
 
  n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
  Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
  Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
  Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
[a] Age at Screening.  
[b] Body Mass Index (BMI) (kg/m^2) = Weight (kg) / (Height (m))^2. 
[c] The denominator is the number of females in each dose group. 
[d] Body Surface Area (BSA) (kgxm) = 0.007184 x Weight (kg)^0.425 / (Height (m))^0.725 (Dubois formula). 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                       
Filename: (Specify file name.rtf) 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 17 of 80 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 18 of 80 
 
Protocol Deviations Category 
CPX-POM 
30 mg/m^2 
N=1 
n (%) 
CPX-POM  
[D2] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D3] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D4] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D5] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D6] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D7] mg/m^2 
N=X 
n (%) 
 
 
PROGRAMMING NOTES:  
• 
Categories are from the protocol deviations criteria form, the table only shows examples. 
 
 
 
 
 
 
Protocol: CPX-POM-001 
--- DELIVERY TYPE ---- 
Page 1 of X  
 
Table 14.1-4 – Protocol Deviations 
(Safety Population) 
 
 
 
 
 
  
 
Any Protocol Deviations 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
 
 
 
 
  
 
Inclusion / Exclusion Criteria 
   INCL01 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
   <cont.> 
 
 
 
 
  
 
Prohibited Medications 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
 
 
 
 
  
 
<cont.>  
 
A patient could be counted under more than one category. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                           
Filename: (Specify file name.rtf) 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 19 of 80 
 
Protocol: CPX-POM-001 
           --- DELIVERY TYPE ---- 
Page 1 of 2 
 
Table 14.1-5.1 – Disease Characteristics 
(Safety Population) 
 
 
CPX-POM 
30 mg/m^2 
N=1 
CPX-POM  
[D2] mg/m^2 
N=X 
CPX-POM  
[D3] mg/m^2 
N=X 
CPX-POM  
[D4] mg/m^2 
N=X 
CPX-POM  
[D5] mg/m^2 
N=X 
CPX-POM  
[D6] mg/m^2 
N=X 
CPX-POM  
[D7] mg/m^2 
N=X 
Cancer Type? [n (%)] 
  Solid Tumor 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Lymphoma 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Solid Tumor Organ Site [n (%)] 
  Lung 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Breast 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Colon 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Prostate 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Time since first diagnosis of Cancer (months) 
Disease Stage at the Cancer diagnosis date? [n (%)] 
  1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Disease Stage at Screening visit date? [n (%)] 
  1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
  Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
  Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
  Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 20 of 80 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                        
Filename: (Specify file name.rtf) 
Protocol: CPX-POM-001 
           --- DELIVERY TYPE ---- 
Page 2 of 2  
 
Table 14.1-5.1 – Disease Characteristics 
(Safety Population) 
 
 
CPX-POM 
30 mg/m^2 
N=1 
CPX-POM  
[D2] mg/m^2 
N=X 
CPX-POM  
[D3] mg/m^2 
N=X 
CPX-POM  
[D4] mg/m^2 
N=X 
CPX-POM  
[D5] mg/m^2 
N=X 
CPX-POM  
[D6] mg/m^2 
N=X 
CPX-POM  
[D7] mg/m^2 
N=X 
Presence of metastases? [n (%)] 
  No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Time between date of Metastatic diagnosis and date of Cycle 1 visit Day 1 (months) 
Extent of current Metastatic disease 
  Bone? [n (%)] 
    No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Lungs? [n (%)] 
    No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Liver? [n (%)] 
    No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Pelvic Lymph Nodes? [n (%)] 
    No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Extrapelvic Lymph Nodes? [n (%)] 
    No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Other? [n (%)] 
    No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
  Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
  Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
  Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 21 of 80 
 
    Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                        
Filename: (Specify file name.rtf) 
 
Protocol: CPX-POM-001 
 
           --- DELIVERY TYPE ---- 
 
Page 1 of X 
 
Table 14.1-5.2 – Other Medical History 
(Safety Population) 
 
System Organ Class/ 
  Preferred Term  
CPX-POM 
30 mg/m^2 
N=1 
n (%) 
CPX-POM  
[D2] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D3] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D4] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D5] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D6] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D7] mg/m^2 
N=X 
n (%) 
condition? 
 
 
 
 
 
 
 
 
System Organ Class #1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred Term #1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred Term #2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred Term #3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  <etc> 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
System Organ Class #2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred Term #1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred Term #2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred Term #3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  <etc> 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
If there was more than one condition reported under the same System Organ Class and Preferred Term, the patient was counted only 
once under that System Organ Class and Preferred Term. If there was more than one condition reported under the same System Organ 
Class, the patient was counted only once under that System Organ Class. 
MedDRA version <version number>. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                          
Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES:  
• 
The Primary System Organ Classes are presented by alphabetical order and the Preferred Terms are sorted within Primary 
System Organ Classes by alphabetical order. 
 
At least one other previous  
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 22 of 80 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 23 of 80 
 
 
Protocol: CPX-POM-001 
 
            --- DELIVERY TYPE ---- 
 
Page 1 of X 
 
 
Table 14.1-6.1.1 – Prior Medications by Therapeutic Class and Preferred Term 
(Safety Population) 
 
Therapeutic Class/ 
  Preferred Term  
CPX-POM 
30 mg/m^2 
N=1 
n (%) 
CPX-POM  
[D2] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D3] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D4] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D5] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D6] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D7] mg/m^2 
N=X 
n (%) 
 
 
 
 
 
 
 
 
Therapeutic Class #1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred Term #1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred Term #2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred Term #3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  <etc> 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
Therapeutic Class #2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred Term #1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred Term #2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred Term #3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  <etc> 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
A prior medication is a medication whose end date is before the date of first CPX-POM dose. 
If there was more than one prior medication reported under the same Therapeutic Class and Preferred Term, the patient was counted 
only once under that Therapeutic Class and Preferred Term. If there was more than one prior medication reported under the same 
Therapeutic Class, the patient was counted only once under that Therapeutic Class. 
WHO-DRUG version <version number>. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                          
Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES:  
• 
The Therapeutic Classes are presented by alphabetical order and the Preferred Terms are sorted within Therapeutic Classes 
by alphabetical order. 
• 
A medication / therapy can appear within more than one Therapeutic Class. 
 
At least one prior medication? 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 24 of 80 
 
 
 
 
Replicate of Table 14.1-6.1.1 
 
PROGRAMMING NOTES:  
• 
Update foootnote: replace ‘A prior medication is a medication whose end date is before the date of first CPX-POM dose’ by 
‘A concomitant medication is a medication that started before the date of first dose and stopped on (or is ongoing after) 
the date of first dose OR a medication whose start date is either the same as (or after) the date of first dose’. 
• 
Update ‘At least one prior medication’ by ‘At least one concomitant medication’. 
• 
The Therapeutic Classes are presented by alphabetical order and the Preferred Terms are sorted within Therapeutic Classes 
by alphabetical order. 
• 
A medication / therapy can appear within more than one Therapeutic Class. 
 
 
 
Table 14.1-6.1.2 – Concomitant Medications by Therapeutic Class and Preferred Term 
(Safety Population) 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 25 of 80 
 
Protocol: CPX-POM-001 
            --- DELIVERY TYPE ---- 
Page 1 of 1 
 
Table 14.1-7 – Overall Exposure to Study Drug and Drug Compliance 
(Safety Population) 
 
 
CPX-POM 
30 mg/m^2 
N=1 
CPX-POM  
[D2] mg/m^2 
N=X 
CPX-POM  
[D3] mg/m^2 
N=X 
CPX-POM  
[D4] mg/m^2 
N=X 
CPX-POM  
[D5] mg/m^2 
N=X 
CPX-POM  
[D6] mg/m^2 
N=X 
CPX-POM  
[D7] mg/m^2 
N=X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Drug Exposure (mg) [b] 
  n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
  Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
  SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
 
  Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
  Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
  Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
 
 
 
 
[a] The CPX-POM exposure expressed in days is defined as the number of days between the first dose taken date and the last dose 
taken date + 1 day. 
[b] The CPX-POM exposure expressed in mg is defined as: dose per m^2 x Body Surface Area x CPX-POM exposure expressed in days. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                             
Filename: (Specify file name.rtf) 
 
 
 
Study Drug Exposure (days) [a] 
  n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
  Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
  Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
  Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 26 of 80 
 
Protocol: CPX-POM-001 
           --- DELIVERY TYPE ---- 
Page 1 of 2 
 
Table 14.2.1 – Patients who have had at least one other post-baseline tumor assessment 
(Efficacy Population) 
 
 
 
CPX-POM 
30 mg/m^2 
N=1 
CPX-POM  
[D2] mg/m^2 
N=X 
CPX-POM  
[D3] mg/m^2 
N=X 
CPX-POM  
[D4] mg/m^2 
N=X 
CPX-POM  
[D5] mg/m^2 
N=X 
CPX-POM  
[D6] mg/m^2 
N=X 
CPX-POM  
[D7] mg/m^2 
N=X 
At least one other post-baseline 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
tumor assessment 
Primary Tumor Site [n (%)] 
 
 
 
 
 
 
 
  Primary Tumor Site #1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Primary Tumor Site #2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Primary Tumor Site #3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
<etc> 
 
 
 
 
 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                        
Filename: (Specify file name.rtf) 
PROGRAMMING NOTES:  
• 
A last column with the header ‘CPX-POM All Doses’ will also be displayed.  
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 27 of 80 
 
Protocol: CPX-POM-001 
           --- DELIVERY TYPE ---- 
Page 1 of 2 
 
Table 14.2.2 – Summary of Patients Responses 
(Efficacy Population) 
 
 
Visit/ 
  Type of Response 
CPX-POM 
30 mg/m^2 
N=1 
CPX-POM  
[D2] mg/m^2 
N=X 
CPX-POM  
[D3] mg/m^2 
N=X 
CPX-POM  
[D4] mg/m^2 
N=X 
CPX-POM  
[D5] mg/m^2 
N=X 
CPX-POM  
[D6] mg/m^2 
N=X 
CPX-POM  
[D7] mg/m^2 
N=X 
Cycle 2-Day 1 Visit 
  Target Lesion Response [n (%)] 
    Complete Response 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Partial Response 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Stable Disease  
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Progressive Disease  
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Not evaluable 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
  Non-Target Lesion Response [n (%)] 
    Complete Response 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Partial Response 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Stable Disease  
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Progressive Disease  
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Not evaluable 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
  Overall Response [n (%)] 
    Complete Response 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Partial Response 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Stable Disease  
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Progressive Disease  
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Not evaluable 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
<repeat for Day 1 visit of each cycle from Cycle 3 to last Cycle number over all patients> 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                        
Filename: (Specify file name.rtf) 
PROGRAMMING NOTES:  
• 
A last column with the header ‘CPX-POM All Doses’ will also be displayed.  


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 28 of 80 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 29 of 80 
 
Protocol: CPX-POM-001 
              --- DELIVERY TYPE ---- 
Page 1 of 1 
 
Table 14.3-1.1 – Overview of Adverse Events 
(Safety Population) 
 
 
CPX-POM 
30 mg/m^2 
N=1 
n (%) 
CPX-POM  
[D2] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D3] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D4] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D5] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D6] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D7] mg/m^2 
N=X 
n (%) 
 
 
 
 
 
 
 
 
Number of patients with  
at least one: 
 
 
 
 
 
 
 
  AE 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  TEAE * 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Related TEAE 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  TEAE leading to discontinuation 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Related TEAE leading to  
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  discontinuation 
 
 
 
 
 
 
 
  Serious TEAE 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Serious related TEAE 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  
 
 
 
 
 
 
 
* A treatment-emergent adverse events (TEAE) is defined as an adverse event which started on or after the first dose of CPX-POM 
administration.  
MedDRA version <version number>. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                    
Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES:  
• 
“Leading to discontinuation” is derived from action taken = permanently discontinued. 
• 
A last column with the header ‘CPX-POM All Doses’ will also be displayed.  
 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 30 of 80 
 
 
Protocol: CPX-POM-001 
          --- DELIVERY TYPE ---- 
Page 1 of X 
 
Table 14.3-1.2 – Number (%) of Patients with Treatment-Emergent Adverse Events by System Organ Class and Preferred Term 
(Safety Population) 
 
System Organ Class/ 
  Preferred Term    
CPX-POM 
30 mg/m^2 
N=1 
n (%) 
CPX-POM  
[D2] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D3] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D4] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D5] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D6] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D7] mg/m^2 
N=X 
n (%) 
 
 
 
 
 
 
 
 
Number of patients with 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
at least one TEAE 
 
System Organ Class #1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred Term #1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred Term #2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred Term #3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  <etc> 
System Organ Class #2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred Term #1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred Term #2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred Term #3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  <etc> 
 
 
 
 
 
 
 
 
If there was more than one TEAE reported under the same System Organ Class and Preferred Term, the patient was counted only once 
under that System Organ Class and that Preferred Term. If there was more than one TEAE reported under the same System Organ Class, 
the patient was counted only once under that System Organ Class. 
MedDRA version <version number>. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                    
Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES:  
• 
The System Organ Classes are presented by decreasing frequency (within the total column – all CPX-POM doses groups combined 
– not displayed) and the Preferred Terms within a System Organ Class are presented by decreasing frequency (within the 
total column – all CPX-POM doses groups combined – not displayed). 
 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 31 of 80 
 
 
Table 14.3-1.3 – Number (%) of Patients with Related Treatment-Emergent Adverse Events by System Organ Class and Preferred Term 
(Safety Population) 
 
Replicate of Table 14.3-1.2 
 
 
Table 14.3-1.4 – Number (%) of Patients with Serious Treatment-Emergent Adverse Events by System Organ Class and Preferred Term 
(Safety Population) 
 
Replicate of Table 14.3-1.2 
 
 
Table 14.3-1.5 – Number (%) of Patients with Serious Related Treatment-Emergent Adverse Events by System Organ Class and 
Preferred Term 
(Safety Population) 
 
Replicate of Table 14.3-1.2 
 
 
Table 14.3-1.6 – Number (%) of Patients with Treatment-Emergent Adverse Events Leading to Discontinuation by System Organ Class 
and Preferred Term 
(Safety Population) 
 
Replicate of Table 14.3-1.2 
 
PROGRAMMING NOTES:  
• 
“Leading to discontinuation” is derived from action taken = permanently discontinued. 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 32 of 80 
 
Protocol: CPX-POM-001 
          --- DELIVERY TYPE ---- 
Page 1 of X  
 
Table 14.3-1.7 – Number (%) of Patients with Treatment-Emergent Adverse Events 
by System Organ Class, Preferred Term and Maximal Severity 
(Safety Population) 
 
System Organ Class/ 
  Preferred Term/ 
    Maximal severity    
CPX-POM 
30 mg/m^2 
N=1 
n (%) 
CPX-POM  
[D2] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D3] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D4] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D5] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D6] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D7] mg/m^2 
N=X 
n (%) 
 
 
 
 
 
 
 
 
Number of patients with any TEAE 
 
 
 
 
 
 
 
    Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Mild 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Moderate 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Severe 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
System Organ Class #1 
 
 
 
 
 
 
 
    Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Mild 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Moderate 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Severe 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred Term #1 
 
 
 
 
 
 
 
    Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Mild 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Moderate 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Severe 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
If there was more than one TEAE reported under the same System Organ Class and Preferred Term, the patient was counted only once 
under the maximal severity for that System Organ Class and Preferred Term. If there was more than one TEAE reported under the 
same System Organ Class, the patient was counted only once under the maximal severity for that System Organ Class. 
MedDRA version <version number>. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                    
Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES:  
• 
Display all severities even if there are no patients. 
• 
The System Organ Classes are presented by decreasing frequency (within the total column – all CPX-POM doses groups combined 
– not displayed) and the Preferred Terms within a System Organ Class are presented by decreasing frequency (within the 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 33 of 80 
 
total column – all CPX-POM doses groups combined – not displayed). 
Table 14.3-1.8 – Number (%) of Patients with Related Treatment-Emergent Adverse Events 
by System Organ Class, Preferred Term and Maximum Severity 
(Safety Population) 
 
 
Replicate of Table 14.3-1.7 
 
 
 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 34 of 80 
 
 
Protocol: CPX-POM-001 
          --- DELIVERY TYPE ---- 
Page 1 of X 
 
Table 14.3-1.9 – Number (%) of Patients with Treatment-Emergent Adverse Events of Special Interest by System Organ Class and 
Preferred Term 
(Safety Population) 
 
System Organ Class/ 
  Preferred Term    
CPX-POM 
30 mg/m^2 
N=1 
n (%) 
CPX-POM  
[D2] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D3] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D4] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D5] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D6] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D7] mg/m^2 
N=X 
n (%) 
 
 
 
 
 
 
 
 
Number of patients with at least 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
one TEAE of Special Interest 
 
 
 
 
 
 
 
 
System Organ Class #1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred Term #1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred Term #2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred Term #3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  <etc> 
 
 
 
 
 
 
 
 
System Organ Class #2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred Term #1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred Term #2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred Term #3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  <etc> 
 
 
 
 
 
 
 
 
 
 
 
 
 
The TEAEs of Special Interest are the clinically significant ophthalmological abnormalities. 
If there was more than one TEAE of Special Interest reported under the same System Organ Class and Preferred Term, the patient 
was counted only once under that System Organ Class and that Preferred Term. If there was more than one TEAE of Special Interest 
reported under the same System Organ Class, the patient was counted only once under that System Organ Class. 
MedDRA version <version number>. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                    
Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES:  
• 
The System Organ Classes are presented by decreasing frequency for all CPX-POM doses groups combined and the Preferred 
Terms within a System Organ Class are presented by decreasing frequency for all CPX-POM doses groups combined. 
• 
A last column with the header ‘CPX-POM All Doses’ will also be displayed. 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 35 of 80 
 
 
Protocol: CPX-POM-001 
    --- DELIVERY TYPE ---- 
Page 1 of X 
Table 14.3-2.1.1 – Summary of Hematology Laboratory Data  
(Safety Population) 
 
Laboratory Parameter: Hemoglobin (unit) 
 
CPX-POM 
30 mg/m^2 
N=1 
CPX-POM  
[D2] mg/m^2 
N=X 
CPX-POM  
[D3] mg/m^2 
N=X 
CPX-POM  
[D4] mg/m^2 
N=X 
CPX-POM  
[D5] mg/m^2 
N=X 
CPX-POM  
[D6] mg/m^2 
N=X 
CPX-POM  
[D7] mg/m^2 
N=X 
Baseline [a] 
 
 
 
 
 
 
 
  n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
  Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
  Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
  Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Cycle 1-Day 4 
 
 
 
 
  n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
  Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
  Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
  Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Change from Baseline  
to Cycle 1-Day 4 
  n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
  Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
  Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
  Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
<repeat for Cycle 1 Day 10 visit> 
<for Cycle 2 to last-1 Cycle, repeat for Day 1 visit and Day 4 visit> 
<for the last Cycle, repeat for Day 22 visit and Day 28 follow-up visit>   
[a] Baseline was the last value/result of assessment prior to or on day of first study treatment. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                          Filename: (Specify file name.rtf) 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 36 of 80 
 
PROGRAMMING NOTES:  
• 
Repeat for all hematology parameters: Hemoglobin, Hematocrit, Platelet count, RBC count, Reticulocytes, WBC Count with 
Differential, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils. 
Protocol: CPX-POM-001 
   --- DELIVERY TYPE ---- 
Page 1 of X 
 
Table 14.3-2.1.2 – Outside of Normal Range - Shift Table for Hematology Laboratory Parameters 
(Safety Population) 
 
Dose group : CPX-POM 30 mg/m^2 (N=1) 
Parameter/ 
  Visit 
Value 
at Visit 
Baseline [a] value 
Low 
n (%) 
Normal 
n (%) 
High 
n (%) 
Low/High*  
n (%) 
 
Total 
Hemoglobin (unit) 
 
 
 
 
 
 
  Cycle 1-Day 4 (N**=XX) 
Low 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
Normal 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
High 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
Low/High* 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
Total 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX  
   
  Cycle 1-Day 10 (N**=XX) 
Low 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
Normal 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
High 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
Low/High* 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
Total 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX  
<for Cycle 2 to last-1 Cycle, repeat for Day 1 visit and Day 4 visit> 
<for the last Cycle, repeat for Day 22 visit and Day 28 follow-up visit>   
<repeat for all doses groups> 
Percentage was based on the number of patients present at each visit with non-missing results for the considered parameter. 
* Included patients with Low or High results. ** Denominator of the percentage. 
[a] Baseline was the last value/result of assessment prior to or on day of first study treatment intake. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
PROGRAMMING NOTES:  
• 
Repeat for all doses groups. 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 37 of 80 
 
• 
Repeat for all hematology parameters: Hemoglobin, Hematocrit, Platelet count, RBC count, Reticulocytes, WBC Count with 
Differential, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils. 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 38 of 80 
 
Protocol: CPX-POM-001 
         --- DELIVERY TYPE ---- 
Page 1 of X 
 
Table 14.3-2.1.3 – Clinician Assessment - Shift Table for Hematology Laboratory Parameters 
(Safety Population) 
 
Dose group : CPX-POM 30 mg/m^2 (N=1) 
Parameter/ 
  Visit 
Value 
at Visit 
                    Baseline [a] value 
Normal 
n (%) 
Abnormal, NCS 
n (%) 
Abnormal, CS 
n (%) 
 
Total 
Hemoglobin (unit) 
 
 
 
 
 
  Cycle 1-Day 4 (N*=XX) 
Normal 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
Abnormal, NCS 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
Abnormal, CS 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
Total 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX  
 
  Cycle 1-Day 10 (N*=XX) 
Normal 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
Abnormal, NCS 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
Abnormal, CS 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
Total 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX  
<for Cycle 2 to last-1 Cycle, repeat for Day 1 visit and Day 4 visit> 
<for the last Cycle, repeat for Day 22 visit and Day 28 follow-up visit>  
<repeat for the other hematology parameters>  
<repeat for all doses groups> 
Percentage was based on the number of patients present at each visit with non-missing results for the considered parameter. 
* Denominator of the percentage. 
[a] Baseline was the last value/result of assessment prior to or on day of first study treatment. 
CS = Clinically Significant; NCS = Not Clinically Significant. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 
 
PROGRAMMING NOTES:  
• 
Repeat for all doses groups. 
• 
Repeat for all hematology parameters: Hemoglobin, Hematocrit, Platelet count, RBC count, Reticulocytes, WBC Count with 
Differential, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils. 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 39 of 80 
 
 
Protocol: CPX-POM-001 
         --- DELIVERY TYPE ---- 
Page 1 of X 
 
Table 14.3-2.1.4 – On-study Hematology Adverse Events: Worst NCI-CTCAE Grade per patient 
(Safety Population) 
 
Parameter/ 
    Worst NCI-CTCAE grade 
CPX-POM 
30 mg/m^2 
N=1 
n (%) 
CPX-POM  
[D2] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D3] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D4] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D5] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D6] mg/m^2 
N=X 
n (%) 
CPX-POM  
[D7] mg/m^2 
N=X 
n (%) 
Hemoglobin (unit) 
  Normal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Grade 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Grade 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Grade 3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Grade 4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Missing 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Hematocrit (unit) 
  Normal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Grade 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Grade 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Grade 3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Grade 4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Missing 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
<repeat for the other hematology parameters> 
 
For a given laboratory parameter, a patient must have at least one on-study grade assessed to be included. 
For a given laboratory parameter, the number of treated patients with at least one on-study grade assessed for that parameter 
will be used as the denominator for the calculation of percentages.  
A patient with multiple results for a parameter will only be counted under the maximum NCI-CTCAE grade for this parameter. 
Laboratory ranges are based on NCI-CTCAE version 4.0. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES:  
• 
Repeat for all hematology parameters: Hemoglobin, Hematocrit, Platelet count, RBC count, Reticulocytes, WBC Count with 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 40 of 80 
 
Differential, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils. 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 41 of 80 
 
 
Protocol: CPX-POM-001 
 
              --- DELIVERY TYPE ---- 
 
Page 1 of X 
 
Table 14.3-2.1.5 – Shift table of Worst NCI-CTCAE Grade for Hematological parameters 
(Safety Population) 
 
Parameter 
Baseline 
grade 
Worst NCI-CTCAE grade 
Normal 
n (%) 
Grade 1 
n (%) 
Grade 2 
n (%) 
Grade 3  
n (%) 
Grade 4  
n (%) 
Missing  
n (%) 
Total  
n (%) 
 
 
 
 
 
 
 
Hematocrit (unit)  Normal 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
  
Grade 1 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
Grade 2 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
Grade 3 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
Grade 4 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
Missing 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
Total 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
Hemoglobin (unit)  Normal 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
  
Grade 1 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
Grade 2 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
Grade 3 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
Grade 4 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
Missing 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
Total 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
<repeat for the other hematology parameters> 
For a given laboratory parameter, a patient must have at least one baseline and one on-treatment grades assessed to be included. 
For a given laboratory parameter, the number of treated patients with at least one baseline and one on-treatment grades assessed 
for that parameter will be used as the denominator for the calculation of percentages.  
A patient with multiple results for a parameter will only be counted under the maximum NCI-CTCAE grade for this parameter. 
Laboratory ranges are based on NCI-CTCAE version 4.0. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
PROGRAMMING NOTES:  
• 
Repeat for all hematology parameters: Hemoglobin, Hematocrit, Platelet count, RBC count, Reticulocytes, WBC Count with 
Differential, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils. 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 42 of 80 
 
Table 14.3-2.2.1 – Summary of Clinical Chemistry Laboratory Data  
(Safety Population) 
 
Replicate of Table 14.3-2.1.1 
 
PROGRAMMING NOTES:  
Clinical Chemistry parameters are: Potassium, Sodium, Chloride, Glucose, BUN, Creatinine, Creatinine clearance, ALP, ALT, AST, 
GGT, Alkaline phosphatase, Direct bilirubin, Indirect bilirubin, Total bilirubin, Total protein, Albumin, Calcium, Bicarbonate, 
Magnesium, Phosphate, Lipase, Amylase 
 
 
Table 14.3-2.2.2 – Outside of Normal Range - Shift Table for Clinical Chemistry Laboratory Parameters 
(Safety Population) 
 
Replicate of Table 14.3-2.1.2 
 
PROGRAMMING NOTES:  
Clinical Chemistry parameters are: Potassium, Sodium, Chloride, Glucose, BUN, Creatinine, Creatinine clearance, ALP, ALT, AST, 
GGT, Alkaline phosphatase, Direct bilirubin, Indirect bilirubin, Total bilirubin, Total protein, Albumin, Calcium, Bicarbonate, 
Magnesium, Phosphate, Lipase, Amylase 
 
 
 
Table 14.3-2.2.3 – Clinician Assessment - Shift Table for Clinical Chemistry Laboratory Parameters 
(Safety Population) 
 
Replicate of Table 14.3-2.1.3 
PROGRAMMING NOTES:  
Clinical Chemistry parameters are: Potassium, Sodium, Chloride, Glucose, BUN, Creatinine, Creatinine clearance, ALP, ALT, AST, 
GGT, Alkaline phosphatase, Direct bilirubin, Indirect bilirubin, Total bilirubin, Total protein, Albumin, Calcium, Bicarbonate, 
Magnesium, Phosphate, Lipase, Amylase 
 
Table 14.3-2.2.4 – On-study Clinical Chemistry Adverse Events: Worst NCI-CTCAE Grade per patient 
(Safety Population) 
 
Replicate of Table 14.3-2.1.4 
PROGRAMMING NOTES:  
Clinical Chemistry parameters are: Potassium, Sodium, Chloride, Glucose, BUN, Creatinine, Creatinine clearance, ALP, ALT, AST, 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 43 of 80 
 
GGT, Alkaline phosphatase, Direct bilirubin, Indirect bilirubin, Total bilirubin, Total protein, Albumin, Calcium, Bicarbonate, 
Magnesium, Phosphate, Lipase, Amylase 
Table 14.3-2.2.5 – Shift table of Worst NCI-CTCAE Grade for Clinical Chemistry Laboratory parameters 
(Safety Population) 
 
Replicate of Table 14.3-2.1.5 
PROGRAMMING NOTES:  
Clinical Chemistry parameters are: Potassium, Sodium, Chloride, Glucose, BUN, Creatinine, Creatinine clearance, ALP, ALT, AST, 
GGT, Alkaline phosphatase, Direct bilirubin, Indirect bilirubin, Total bilirubin, Total protein, Albumin, Calcium, Bicarbonate, 
Magnesium, Phosphate, Lipase, Amylase 
 
 
 
Table 14.3-2.3.1 – Summary of Coagulation Laboratory Data  
(Safety Population) 
 
Replicate of Table 14.3-2.1.1 
 
PROGRAMMING NOTES:  
• 
Coagulation parameters are PT and aPTT. 
• 
Only Day 1 visit of each cycle 
 
 
 
Table 14.3-2.4 – Summary of Thyroid Panel Laboratory Data  
(Safety Population) 
 
Replicate of Table 14.3-2.1.1 
 
PROGRAMMING NOTES:  
• 
Coagulation parameters are TSH, Free T4 and Free and total T3 
• 
Only Day 1 visit of each cycle 
 
 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 44 of 80 
 
 
Table 14.3-2.5.1 – Summary of Urinalysis Laboratory Data  
(Safety Population) 
 
Replicate of Table 14.3-2.1.1 
 
PROGRAMMING NOTES:  
• 
Urinalysis parameters are Color, Turbidity, pH, Specific gravity, Glucose, Ketones, Nitrites, Bilirubin, Urobilirubin, 
Protein, RBCs, WBCs, Epithelial cells, Casts, Crystals, Bacteria, eGFR (Screening only) 
• 
Replace ‘Day 4’ by ‘Day 5’ for each cycle 
 
 
Table 14.3-2.5.2 – Outside of Normal Range - Shift Table for Urinalysis Laboratory Parameters 
(Safety Population) 
 
Replicate of Table 14.3-2.1.2 
 
PROGRAMMING NOTES:  
• 
Urinalysis parameters are Color, Turbidity, pH, Specific gravity, Glucose, Ketones, Nitrites, Bilirubin, Urobilirubin, 
Protein, RBCs, WBCs, Epithelial cells, Casts, Crystals, Bacteria, eGFR (Screening only) 
• 
Replace ‘Day 4’ by ‘Day 5’ for each cycle 
 
 
Table 14.3-2.5.3 – Clinician Assessment - Shift Table for Urinalysis Laboratory Parameters 
(Safety Population) 
 
Replicate of Table 14.3-2.1.3 
 
PROGRAMMING NOTES:  
• 
Urinalysis parameters are Color, Turbidity, pH, Specific gravity, Glucose, Ketones, Nitrites, Bilirubin, Urobilirubin, 
Protein, RBCs, WBCs, Epithelial cells, Casts, Crystals, Bacteria, eGFR (Screening only) 
• 
Replace ‘Day 4’ by ‘Day 5’ for each cycle 
 
 
Table 14.3-2.5.4 – On-study Urinalysis Adverse Events: Worst NCI-CTCAE Grade per patient 
(Safety Population) 
 
Replicate of Table 14.3-2.1.4 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 45 of 80 
 
 
PROGRAMMING NOTES:  
• 
Urinalysis parameters are Color, Turbidity, pH, Specific gravity, Glucose, Ketones, Nitrites, Bilirubin, Urobilirubin, 
Protein, RBCs, WBCs, Epithelial cells, Casts, Crystals, Bacteria, eGFR (Screening only) 
• 
Replace ‘Day 4’ by ‘Day 5’ for each cycle 
 
 
Table 14.3-2.5.5 – Shift table of Worst NCI-CTCAE Grade for Urinalysis Laboratory parameters 
(Safety Population) 
 
Replicate of Table 14.3-2.1.5 
 
PROGRAMMING NOTES:  
• 
Urinalysis parameters are Color, Turbidity, pH, Specific gravity, Glucose, Ketones, Nitrites, Bilirubin, Urobilirubin, 
Protein, RBCs, WBCs, Epithelial cells, Casts, Crystals, Bacteria, eGFR (Screening only) 
• 
Replace ‘Day 4’ by ‘Day 5’ for each cycle 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 46 of 80 
 
Protocol: CPX-POM-001 
            --- DELIVERY TYPE ---- 
Page 1 of 1  
 
Table 14.3-2.6 – Summary of Other Laboratory Data  
(Safety Population) 
 
Visit/ 
  Parameter 
CPX-POM 
30 mg/m^2 
N=1 
CPX-POM  
[D2] mg/m^2 
N=X 
CPX-POM  
[D3] mg/m^2 
N=X 
CPX-POM  
[D4] mg/m^2 
N=X 
CPX-POM  
[D5] mg/m^2 
N=X 
CPX-POM  
[D6] mg/m^2 
N=X 
CPX-POM  
[D7] mg/m^2 
N=X 
Screening visit 
  HIV? [n (%)] 
    No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Hepatitis A? [n (%)] 
    No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Hepatitis B? [n (%)] 
    No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Hepatitis C? [n (%)] 
    No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Pregnancy test? [n (%)] 
    No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Cycle 1-Day 1 
  Pregnancy test? [n (%)] 
    No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
<for Pregnancy test, repeat for Day 1 visit of each cycle> 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                        
Filename: (Specify file name.rtf) 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 47 of 80 
 
 
 
Table 14.3-3.1 – Summary of Vital Signs  
(Safety Population) 
 
Replicate of Table 14.3-2.1.1 
 
PROGRAMMING NOTES:  
• 
Update “laboratory parameter” by “parameter”  
• 
Vital signs include pulse rate, blood pressure, respiratory rate, oxygen saturation and temperature 
• 
On Days 1 and 5, vital signs are measured at pre-dose and at 6-hour intervals post-dose. 
 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 48 of 80 
 
Protocol: CPX-POM-001 
--- DELIVERY TYPE ---- 
Page 1 of 3  
 
Table 14.3-3.2 – Summary of Abnormal Vital Signs 
(Safety Population) 
 
Parameter/  
  Visit/ 
    Category 
CPX-POM  
30 mg/m^2 
N=1 
CPX-POM  
[D2] mg/m^2 
N=X 
CPX-POM  
[D3] mg/m^2 
N=X 
CPX-POM  
[D4] mg/m^2 
N=X 
CPX-POM  
[D5] mg/m^2 
N=X 
CPX-POM  
[D6] mg/m^2 
N=X 
CPX-POM  
[D7] mg/m^2 
N=X 
Pulse rate (bpm) 
 
  Cycle 1 
 
    Baseline [a]* 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
      > 150 bpm 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
      [101-150] bpm 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
      < 55 bpm 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
 
 
 
 
 
 
 
    Cycle 1-Day 2 * 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
      > 150 bpm 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
      [101-150] bpm 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
      < 55 bpm 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
<repeat for next Cycle 1 visits> 
<for Cycle 2 to last-1 Cycle, repeat for Day 1 visit to Day 6 visit> 
<for the last Cycle, repeat for Day 1 visit to Day 6 visit, Day 22 visit and Day 28 follow-up visit> 
 
* Denominator for the percentages. 
[a] Baseline was the last value/result of assessment prior to or on day of first study treatment. 
> 150 bpm: Very High values 
[101-150] bpm: High values 
< 55 bpm: Low values 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                       
Filename: (Specify file name.rtf) 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 49 of 80 
 
Protocol: CPX-POM-001 
    --- DELIVERY TYPE ---- 
Page 2 of 3 
 
Table 14.3-3.2 – Summary of Abnormal Vital Signs 
(Safety Population) 
 
Parameter/  
  Visit/ 
    Category 
CPX-POM  
30 mg/m^2 
N=1 
CPX-POM  
[D2] mg/m^2 
N=X 
CPX-POM  
[D3] mg/m^2 
N=X 
CPX-POM  
[D4] mg/m^2 
N=X 
CPX-POM  
[D5] mg/m^2 
N=X 
CPX-POM  
[D6] mg/m^2 
N=X 
CPX-POM  
[D7] mg/m^2 
N=X 
 
Systolic Blood Pressure (mmHg) 
 
  Baseline [a]* 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
    >= 161 mmHg 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
    [131-160] bpm 
 XX (XXX.X)  XX (XXX.X)  XX (XXX.X)  XX (XXX.X)  XX (XXX.X) 
XX (XXX.X)   XX (XXX.X) 
    < 95 mmHg 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
 
 
 
 
 
 
 
  Cycle 1-Day 2 * 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
    >= 161 mmHg 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
    [131-160] bpm 
 XX (XXX.X)  XX (XXX.X)  XX (XXX.X)  XX (XXX.X)  XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
    < 95 mmHg 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
 
 
 
 
 
 
 
<repeat for next Cycle 1 visits> 
<for Cycle 2 to last-1 Cycle, repeat for Day 1 visit to Day 6 visit> 
<for the last Cycle, repeat for Day 1 visit to Day 6 visit, Day 22 visit and Day 28 follow-up visit> 
 
* Denominator for the percentages. 
[a] Baseline was the last value/result of assessment prior to or on day of first study treatment. 
>= 161 bpm: Very High values 
[131-160] bpm: High values 
< 95 bpm: Low values 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                        
Filename: (Specify file name.rtf) 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 50 of 80 
 
Protocol: CPX-POM-001 
        --- DELIVERY TYPE ---- 
Page 3 of 3  
 
Table 14.3-3.2 – Summary of Abnormal Vital Signs 
(Safety Population) 
 
Parameter/  
  Visit/ 
    Category 
CPX-POM  
30 mg/m^2 
N=1 
CPX-POM  
[D2] mg/m^2 
N=X 
CPX-POM  
[D3] mg/m^2 
N=X 
CPX-POM  
[D4] mg/m^2 
N=X 
CPX-POM  
[D5] mg/m^2 
N=X 
CPX-POM  
[D6] mg/m^2 
N=X 
CPX-POM  
[D7] mg/m^2 
N=X 
 
Diastolic Blood Pressure (mmHg) 
 
  Baseline [a]* 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
    >= 101 mmHg 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
    [86-100] bpm 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
    < 50 mmHg 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
 
 
 
 
 
 
 
  Cycle 1-Day 2 * 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
    >= 101 mmHg 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
    [86-100] bpm 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
    < 50 mmHg 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
<repeat for next Cycle 1 visits> 
<for Cycle 2 to last-1 Cycle, repeat for Day 1 visit to Day 6 visit> 
<for the last Cycle, repeat for Day 1 visit to Day 6 visit, Day 22 visit and Day 28 follow-up visit> 
 
* Denominator for the percentages. 
[a] Baseline was the last value/result of assessment prior to or on day of first study treatment. 
>= 101 bpm: Very High values 
[86-100] bpm: High values 
< 50 bpm: Low values 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                       
Filename: (Specify file name.rtf) 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 51 of 80 
 
 
 
Table 14.3-4.1 – Summary of ECG Parameters 
(Safety Population) 
 
Replicate of Table 14.3-2.1.1 
 
PROGRAMMING NOTES:  
• 
Update “laboratory parameter” by “ECG parameter”  
• 
Include all ECG parameters 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 52 of 80 
 
 
Protocol: CPX-POM-001 
 
          --- DELIVERY TYPE ---- 
 
Page 1 of Y 
 
Table 14.3-4.2 – Summary of Abnormal ECG Intervals 
(Safety Population) 
 
Parameter/  
  Visit/ 
    Category 
CPX-POM  
30 mg/m^2 
N=1 
CPX-POM  
[D2] mg/m^2 
N=X 
CPX-POM  
[D3] mg/m^2 
N=X 
CPX-POM  
[D4] mg/m^2 
N=X 
CPX-POM  
[D5] mg/m^2 
N=X 
CPX-POM  
[D6] mg/m^2 
N=X 
CPX-POM  
[D7] mg/m^2 
N=X 
 
 
 
 
 
 
 
 
Heart rate (bpm) 
 
 
 
 
 
 
 
 
  Baseline [a]* 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
    Normal 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
    Abnormal, NCS 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
    Abnormal, CS 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
 
 
 
 
 
 
 
  Cycle 1-Day 5 * 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
    Normal 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
    Abnormal, NCS 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
    Abnormal, CS 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
<for Cycle 2 to last-1 cycle, repeat for Day 1 visit> 
<for last cycle, repeat for Day 1 visit and Day 28 follow-up visit> 
<repeat for PR interval and QRS interval> 
 
 
 
 
 
 
 
 
 
* Denominator for the percentages. 
[a] Baseline was the last value/result of assessment prior to or on day of first study treatment. 
CS = Clinically Significant; NCS = Not Clinically Significant. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                      
Filename: (Specify file name.rtf) 
 
 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 53 of 80 
 
 
Protocol: CPX-POM-001 
             --- DELIVERY TYPE ---- 
Page X of Y  
 
Table 14.3-4.2 – Summary of Abnormal ECG Intervals 
(Safety Population) 
 
Parameter/  
  Visit/ 
    Category 
CPX-POM  
30 mg/m^2 
N=1 
CPX-POM  
[D2] mg/m^2 
N=X 
CPX-POM  
[D3] mg/m^2 
N=X 
CPX-POM  
[D4] mg/m^2 
N=X 
CPX-POM  
[D5] mg/m^2 
N=X 
CPX-POM  
[D6] mg/m^2 
N=X 
CPX-POM  
[D7] mg/m^2 
N=X 
 
 
 
 
 
 
 
 
QTcB interval (msec) 
 
 
 
 
 
 
 
  Baseline [a]* 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
    > 450 msec 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
    > 480 msec 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
    > 500 msec 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
 
 
 
 
 
 
 
  Cycle 1-Day 5 * 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
    > 450 msec 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
    > 480 msec 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
    > 500 msec 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
  Change from Baseline to  
  Cycle 1-Day 5 * 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
    > 30 msec 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
    > 60 msec 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
<for Cycle 2 to last-1 cycle, repeat for Day 1 visit> 
<for last cycle, repeat for Day 28 follow-up visit> 
<repeat for QTcF interval> 
* Denominator for the percentages. 
[a] Baseline was the last value/result of assessment prior to or on day of first study treatment. 
CS = Clinically Significant; NCS = Not Clinically Significant. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                      
Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES: For QTcF interval, the category ‘> 500 msec’ will be replaced by ‘> 500 msec (CS)’ and the category ‘> 60 msec’ 
will be replaced by ‘> 60 msec (CS)’. 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 54 of 80 
 
 
 
 
 
Protocol: CPX-POM-001 
     --- DELIVERY TYPE ---- 
Page 1 of X  
 
 
Listing 16.1.7-1 – Treatment Administration  
(All Patients) 
 
Center/ 
Patient 
Visit 
CPX-POM  
Dose group  
CPX-POM 
Dose 
Amount 
per 
Prot.? 
If no, Reason 
for Adjustment? 
Total 
Inf. Bag 
vol. of 
Sal. and 
CPX-POM 
(ml) 
Was 
Total  
Vol. 
Inf.? 
If no, 
actual 
Vol. 
Inf.? 
Adm. Date (Day) 
Inf. Start Time- 
Inf. End Time 
Arm 
Used 
for IV 
Infusion 
Interrupted? 
XXXXXXXX 
BAS 
30 mg/m^2 
Yes 
 
XXX 
Yes 
 
DDMMMYYYY (XX) 
HH:MM-HH:MM 
Right 
 
 
C1 TRT D2 
 
30 mg/m^2 
Yes 
 
Yes 
Yes 
 
DDMMMYYYY (XX) 
HH:MM-HH:MM 
Right 
 
 
 
C1 TRT D3 
 
30 mg/m^2 
Yes 
 
XXX 
Yes 
 
DDMMMYYYY (XX) 
HH:MM-HH:MM 
Right 
 
 
C1 TRT D4 
 
30 mg/m^2 
Yes 
 
XXX 
Yes 
 
DDMMMYYYY (XX) 
HH:MM-HH:MM 
Right 
 
 
C1 TRT D5 
 
 
30 mg/m^2 
 
No 
Adverse event 
XXX 
No 
XXX 
DDMMMYYYY (XX) 
HH:MM-HH:MM 
Right 
 
 
Yes [a] 
 
 
<repeat for Days 1,2,3,4 and 5 of next cycles if relevant> 
Prot.: Protocol; Inf.: Infusion/Infused; Vol.: Volume; Sal.: Saline; Adm.: Administration; Inter.: Interruption/Interrupted;  
IV: Intravenous 
[a]: see further details regarding the infusion interruption in Listing 16.1.7-2 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 
 
PROGRAMMING NOTES:  
• 
Listing to be sorted by increasing CPX-POM dose. 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 55 of 80 
 
 
 
 
Protocol: CPX-POM-001 
     --- DELIVERY TYPE ---- 
Page 1 of X  
 
 
Listing 16.1.7-2 – Infusion Interruption  
(All Patients) 
 
Center/ 
Patient 
Visit 
CPX-POM  
Dose group  
Reason for 
Inf. Inter.? 
Specify 
Adm. Date (Day) 
Time Inf. Inter. 
Inf. 
Rest.? 
Time Inf. 
Restarted 
Reason  
for Not 
Restarting? 
Specify 
Inf. 
Site 
React.? 
XXXXXXXX 
C1 TRT D5 30 mg/m^2 
Infusion 
reaction 
XXXXX 
DDMMMYYYY (XX) 
HH:MM 
No 
 
Infusion 
reaction 
XXXXX 
Yes 
XXXXXXXX 
C2 TRT D2 [D2] mg/m^2 Technical 
problem 
XXXXX 
DDMMMYYYY (XX) 
HH:MM 
Yes 
HH:MM 
 
XXXXX 
No 
 
<cont> 
Inf.: Infusion; Inter.: Interrupted; Rest.: Restarted; React.: Reaction. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES:  
• 
Listing to be sorted by increasing CPX-POM dose. 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 56 of 80 
 
Protocol: CPX-POM-001 
--- DELIVERY TYPE ---- 
Page 1 of X  
 
Listing 16.2.1-1.1 – Preface to Inclusion and Exclusion Criteria 
 
Protocol  
Version 
Inclusion/ 
Exclusion No. 
Inclusion / Exclusion Text 
 
 
3.0 
 
 
 
INCL01 
 
 
 
Patient has histologically- or cytologically- confirmed metastatic or advanced-stage solid malignant 
tumor that is refractory to standard therapy. Patients should only be included if no therapy exists 
or if they have received all standard therapies that would be potentially curative or might provide 
significant benefit. 
 
INCL02 
 
 
 
Patient may have received up to 4 prior lines of cytotoxic chemotherapy or immunotherapy for their 
metastatic disease (e.g., docetaxel + doxorubicin ± cyclophosphamide), and also may have received 
additional prior endocrine therapy, as appropriate (e.g., for breast or prostate cancer), or non-
myelosuppressive therapy (e.g., bevacizumab, trastuzumab). 
 
<etc> 
 
 
 
 
 
EXCL01 
 
 
Patient has a history of risk factors for torsade de pointes (e.g., heart failure, hypokalemia, 
family history of long QT syndrome) or requires the use of concomitant medications that prolong the 
QT/QTc interval during study participation. 
 
EXCL02 
 
Patient has an abnormal cardiac appearance/heart size, as evidenced by chest X-ray or computed 
tomography (CT) scan. 
 
<etc> 
 
 
 
 
 
 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES:  
• 
List all Inclusion / Exclusion criteria as per eCRF.  
• 
Note: Inclusion / Exclusion text displayed in the listing shell is based on the text in Protocol Version 3.0. 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 57 of 80 
 
Protocol: CPX-POM-001 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
 
Listing 16.2.1-1.2 – List of Failed Inclusion and Exclusion Criteria 
(All Patients) 
 
 
Center/ 
Patient 
CPX-POM  
Dose group 
Protocol  
Version 
Failed Inclusion / Exclusion 
 
 
 
XXXX 
[D3] mg/m^2 
3.0 
INCL01, INCL09 
 
 
 
EXCL05, EXCL08, EXCl10 
 
XXXX 
[D5] mg/m^2 
3.0 
INCL02 
 
 
 
EXCL03, EXCL07 
 
<to be completed with the other patients having at least one protocol deviation> 
 
 
 
 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES:  
• 
List all Inclusion / Exclusion criteria that are failed (i.e. ‘N’ for inclusion and ‘Y’ for exclusion)  
• 
Listing to be sorted by increasing CPX-POM dose. 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 58 of 80 
 
 
Protocol: CPX-POM-001 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
 
Listing 16.2.1-2 – Patient Disposition 
(All Patients) 
 
Center/ 
Patient 
Country 
 
CPX-POM  
Dose group 
Date (day) of 
Discontinuation/ 
Completion 
Reason for 
Discontinuation 
Date (day) of 
Last Dose 
Date (day) of 
Death 
Reason 
 
 
 
 
 
 
 
XXXX 
XXX 
30 mg/m^2 
DDMMMYYYY (XXX) 
 
DDMMMYYYY (XXX) 
 
 
XXXX 
XXX 
[D2] mg/m^2 
DDMMMYYYY (XXX) 
 
DDMMMYYYY (XXX) 
 
 
XXXX 
XXX 
[D3] mg/m^2 
DDMMMYYYY (XXX) 
 
DDMMMYYYY (XXX) 
 
 
XXXX 
XXX 
[D4] mg/m^2 
DDMMMYYYY (XXX) 
 
DDMMMYYYY (XXX) 
 
 
XXXX 
XXX 
[D4] mg/m^2 
DDMMMYYYY (XXX) 
Adverse Event 
DDMMMYYYY (XXX) 
 
 
XXXX 
XXX 
[D4] mg/m^2 
DDMMMYYYY (XXX) 
 
DDMMMYYYY (XXX) 
 
 
 
 
 
 
 
 
 
 
<etc> 
Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY, -- represents an unknown date 
component. 
   
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 59 of 80 
 
 
 
Protocol: CPX-POM-001 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
 
Listing 16.2.2 – Protocol Deviations 
(All Patients) 
 
Center/ 
Patient 
 
CPX-POM 
Dose group 
Category 
Details 
Leading to Exclusion 
from Analysis 
Population? 
Analysis  
Population(s) 
XXXX 
[D4] mg/m^2 Compliance 
Not treated 
Yes 
SAFETY 
 
 
 
 
 
<to be completed with the other patients having at least one protocol deviation> 
 
 
 
 
 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES:  
• 
Listing to be sorted by increasing CPX-POM dose. 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 60 of 80 
 
Protocol: CPX-POM-001 
 
--- DELIVERY TYPE ---- 
Page 1 of X  
 
Listing 16.2.3-1 – Demographic and Baseline Characteristics 
(All Patients) 
 
Center/ 
Patient Country 
 
 
 
 
CPX-POM  
Dose group 
Date of 
Birth 
 
 
 
 
Age 
(year) 
Sex 
 
 
 
 
 
 
Race 
 
 
 
 
 
Weight 
(kg) 
 
 
 
 
 
Height 
(cm) 
 
 
 
 
 
BMI 
(kg/m^2) 
 
 
 
 
 
BSA 
(kgxm) 
 
 
 
Patient of  
Child 
Bearing 
Potential? 
 
 
 
 
Creat.
Clear. 
(unit) 
XXXX 
XXX 
30 mg/m^2 
DDMMMYYYY XX 
Male 
XXXXX 
XXX.X 
XXX 
XX.X 
XX.X 
 
XXX 
XXXX 
XXX 
[D2] mg/m^2 DDMMMYYYY XX 
Female 
XXXXX 
XXX.X 
XXX 
XX.X 
XX.X 
Yes 
XXX 
XXXX 
XXX 
[D3] mg/m^2 DDMMMYYYY XX 
Female 
XXXXX 
XXX.X 
XXX 
XX.X 
XX.X 
No 
XXX 
XXXX 
XXX 
[D4] mg/m^2 DDMMMYYYY XX 
Male 
XXXXX 
XXX.X 
XXX 
XX.X 
XX.X 
 
XXX 
XXXX 
XXX 
[D4] mg/m^2 DDMMMYYYY XX 
Male 
XXXXX 
XXX.X 
XXX 
XX.X 
XX.X 
 
XXX 
XXXX 
XXX 
[D4] mg/m^2 DDMMMYYYY XX 
Female 
XXXXX 
XXX.X 
XXX 
XX.X 
XX.X 
No 
XXX 
 
<etc> 
 
Creat. Clear.: Creatinine Clearance. 
Dates are displayed as DDMMMYYYY, -- represents an unknown date component. Age was calculated from date of birth and date 
of screening. BMI (kg/m²)= Weight (kg)/(Height (m)^2. BSA (kgxm) = 0.007184 x Weight (kg)^0.425 / (Height (m))^0.725 (Dubois 
formula). 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES:  
• 
Listing to be sorted by increasing CPX-POM dose. 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 61 of 80 
 
Protocol: CPX-POM-001 
 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
 
 
PROGRAMMING NOTES:  
• 
Listing to be sorted by increasing CPX-POM dose. 
 
 
 
 
 
 
 
 
Listing 16.2.3-2 – HIV, Hepatitis and Pregnancy Test Results 
(All Patients) 
 
Center/ 
Patient 
 
 
CPX-POM  
Dose group 
Visit 
 
 
 
Parameter 
Assessment  
Performed? 
Assessment 
Date 
Study  
Day 
 
 
 
Result 
 
XXXX 
30 mg/m^2 
SCR 
HIV 
Yes 
DDMMMYYYY 
XX 
No 
 
 
 
Hepatitis A 
Yes 
DDMMMYYYY 
XX 
No 
 
 
 
Hepatitis B 
Yes 
DDMMMYYYY 
XX 
No 
 
 
 
Hepatitis C 
Yes 
DDMMMYYYY 
XX 
No 
 
 
 
Pregnancy Test 
Yes 
DDMMMYYYY 
XX 
No 
 
 
BAS 
Pregnancy Test 
Yes 
DDMMMYYYY 
XX 
No 
<repeat for Day 1 of next cycles if relevant> 
<cont.> 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
 Filename: (Specify file name.rtf) 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 62 of 80 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 63 of 80 
 
Protocol: CPX-POM-001 
 
--- DELIVERY TYPE ---- 
Page 1 of X  
 
Listing 16.2.4-1 – Cancer History 
(All Patients) 
 
Center/
Patient 
 
 
CPX-POM  
Dose group 
 
 
Cancer  
Type 
 
 
If Other,  
specify 
Initial 
Diagnosis  
Date (Day) 
Disease 
Stage at  
Initial  
Diagnosis 
 
Current  
Disease  
Stage 
 
Pres. 
of 
Metas.? 
Date of 
Metastatic 
Diagnosis (Day) 
 
 
 
Location 
 
 
If Other, 
specify 
XXXX 
30 mg/m^2 
XXXXX 
 
DDMMMYYYY (XXX) Grade X 
Grade X No 
 
 
 
XXXX 
[D2] mg/m^2 XXXXX 
 
DDMMMYYYY (XXX) Grade X 
Grade X No 
 
 
 
XXXX 
[D3] mg/m^2 XXXXX 
 
DDMMMYYYY (XXX) Grade X 
Grade X Yes 
DDMMMYYYY (XXX) 
Bone 
 
XXXX 
[D4] mg/m^2 XXXXX 
 
-----YYYY 
Grade X 
Grade X No 
 
 
 
XXXX 
[D4] mg/m^2 Other 
XXXXX 
DDMMMYYYY (XXX) Grade X 
Grade X Yes 
DDMMMYYYY (XXX) 
Other 
XXXXX 
XXXX 
[D4] mg/m^2 XXXXX 
 
-----YYYY 
Grade X 
Grade X Yes 
DDMMMYYYY (XXX) 
Lungs 
Liver  
 
 
<etc> 
 
 
Pres.: Presence; Metas.: Mestastases 
Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY, -- represents an unknown date 
component. 
 
 
PROGRAMMING NOTES:  
• 
Listing to be sorted by increasing CPX-POM dose. 
 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
 Filename: (Specify file name.rtf) 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 64 of 80 
 
Protocol: CPX-POM-001 
 
--- DELIVERY TYPE ---- 
Page 1 of X  
 
Listing 16.2.4-2 – Prior Cancer Therapies 
(All Patients) 
 
Center/
Patient 
CPX-POM  
Dose group 
Therapy  
Type 
If Radiation,  
specify 
Therapy  
Name 
Line of 
Therapy 
Treatment 
Setting 
Treatment 
Intent 
Start Date (Day) 
End Date (Day) 
Best 
Response 
 
 
XXXX 
30 mg/m^2 
XXXXX 
 
XXXXX 
X 
XXXXX 
XXXXX 
DDMMMYYYY(XX) 
DDMMMYYYY(XX) 
XXXXX 
 
XXXX 
[D2] mg/m^2 XXXXX 
 
XXXXX 
X 
XXXXX 
XXXXX 
DDMMMYYYY(XX) 
DDMMMYYYY(XX) 
XXXXX 
 
XXXX 
[D3] mg/m^2 Radiation 
XXXXX 
XXXXX 
X 
XXXXX 
XXXXX 
DDMMMYYYY(XX) 
DDMMMYYYY(XX) 
XXXXX 
 
<etc> 
 
Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY, -- represents an unknown date 
component. 
 
 
PROGRAMMING NOTES:  
• 
Listing to be sorted by increasing CPX-POM dose. 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
 Filename: (Specify file name.rtf) 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 65 of 80 
 
Protocol: CPX-POM-001 
 
--- DELIVERY TYPE ---- 
Page 1 of X  
 
Listing 16.2.4-3 – Other Medical History 
(All Patients) 
 
CPX-POM Dose Group: 30 mg/m^2 
Center/ 
Patient 
System Organ Class/ 
  Preferred Term/ 
 
    Verbatim 
Start Date (Day) 
End Date (Day) 
Treated 
with 
medication? 
 
 
 
XXXX 
XXXXXX/ 
  XXXXX/ 
    XXXXXXXXXXX 
DDMMMYYYY (XXX) 
DDMMMYYYY (XXX) No 
 
 
 
 
 
XXXX 
XXXXXX/ 
  XXXXX/ 
    XXXXXXXXXXX 
--MMMYYYY 
Ongoing 
Yes 
<cont.> 
 
 
 
 
 
 
 
 
 
Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY, -- represents an unknown date 
component. 
MedDRA <version no.> 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                   
Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES:  
• 
Listing to be sorted by increasing CPX-POM dose. 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 66 of 80 
 
Protocol: CPX-POM-001 
 
--- DELIVERY TYPE ---- 
Page 1 of X  
 
Listing 16.2.4-4 – Cardiac Function 
(All Patients) 
 
Center/
Patient 
 
CPX-POM  
Dose group 
Echocardiogram 
or MUGA Scan 
performed? 
 
Method of 
Assessment 
Date of 
Assessment 
 
Overall 
Interpretation 
 
 
If Abnormal CS, specify 
XXXX 
30 mg/m^2 
Yes 
Echocardiogram 
DDMMMYYYY 
XXXXX 
 
XXXX 
[D2] mg/m^2 
Yes 
MUGA 
DDMMMYYYY 
Abnormal CS 
XXXXX 
XXXX 
[D3] mg/m^2 
Yes 
Echocardiogram 
DDMMMYYYY 
XXXXX 
 
<etc> 
 
 
CS: Clinically Significant. Dates are displayed as DDMMMYYYY, -- represents an unknown date component. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                    
Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES:  
• 
Listing to be sorted by increasing CPX-POM dose. 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 67 of 80 
 
Protocol: CPX-POM-001 
 
--- DELIVERY TYPE ---- 
Page 1 of X  
 
Listing 16.2.4-5 – Ophthalmologic Exam 
(All Patients) 
 
Center/
Patient 
 
CPX-POM  
Dose group 
Ophthalmology 
Assessments 
performed? 
 
Use of 
Corrective 
Lenses? 
Date of 
Assessment 
 
Overall 
Interpretation 
 
 
If Abnormal CS, specify 
XXXX 
30 mg/m^2 
Yes 
Yes 
DDMMMYYYY 
XXXXX 
 
XXXX 
[D2] mg/m^2 
Yes 
No  
DDMMMYYYY 
Abnormal CS 
XXXXX 
XXXX 
[D3] mg/m^2 
Yes 
No 
DDMMMYYYY 
XXXXX 
 
<etc> 
 
 
CS: Clinically Significant. Dates are displayed as DDMMMYYYY, -- represents an unknown date component. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                    
Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES:  
• 
Listing to be sorted by increasing CPX-POM dose. 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 68 of 80 
 
Protocol: CPX-POM-001 
 
--- DELIVERY TYPE ---- 
Page 1 of X  
 
Listing 16.2.4-6 – RECIST Target Lesions 
(All Patients) 
 
Center/
Patient 
 
 
CPX-POM  
Dose group 
Visit/ 
Target Lesions 
Identified at 
Screening Visit? 
Date of 
Scans 
review 
 
 
Lesion  
Number 
 
 
Organ  
Site 
Specific 
Location 
within the 
Organ Site 
 
Lymph  
Node  
Type 
 
 
 
Method 
 
Lesion 
Diameter 
(mm) 
XXXX 
30 mg/m^2 
C1 TRT D1 / Yes 
DDMMMYYYY 
T01 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
 
 
 
 
T02 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXX 
[D2] mg/m^2 
C1 TRT D1 / Yes 
DDMMMYYYY 
T01 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
 
C2 TRT D1 / Yes 
DDMMMYYYY 
T01 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
 
 
 
DDMMMYYYY 
T02 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXX 
[D2] mg/m^2 
C1 TRT D1 / Yes 
DDMMMYYYY 
T01 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
 
C2 TRT D1 / Yes 
DDMMMYYYY 
T01 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
 
C3 TRT D1 / Yes 
DDMMMYYYY 
T01 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
 
<etc> 
 
 
CS: Clinically Significant. Dates are displayed as DDMMMYYYY, -- represents an unknown date component. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                    
Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES:  
• 
Listing to be sorted by increasing CPX-POM dose. 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 69 of 80 
 
Protocol: CPX-POM-001 
 
--- DELIVERY TYPE ---- 
Page 1 of X  
 
Listing 16.2.4-7 – RECIST Non-Target Lesions 
(All Patients) 
 
Center/
Patient 
 
 
 
CPX-POM  
Dose group 
Visit/ 
Non-Target 
Lesions 
Identified at 
Screening Visit? 
Date of 
Scans 
review 
 
 
 
Lesion  
Number 
 
 
 
Organ  
Site 
 
Specific 
Location 
within the 
Organ Site 
 
 
Lymph  
Node  
Type 
 
 
 
 
Method 
 
 
 
 
Result 
XXXX 
30 mg/m^2 
C1 TRT D1 / Yes 
DDMMMYYYY 
NT01 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
 
 
 
 
NT02 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXX 
[D2] mg/m^2 
C1 TRT D1 / Yes 
DDMMMYYYY 
NT01 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
 
C2 TRT D1 / Yes 
DDMMMYYYY 
NT01 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
 
 
 
 
NT02 
NT03 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXX 
[D2] mg/m^2 
C1 TRT D1 / Yes 
DDMMMYYYY 
NT01 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
 
C2 TRT D1 / Yes 
DDMMMYYYY 
NT01 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
 
C3 TRT D1 / Yes 
DDMMMYYYY 
NT01 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
 
<etc> 
 
CS: Clinically Significant. Dates are displayed as DDMMMYYYY, -- represents an unknown date component. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                    
Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES:  
• 
Listing to be sorted by increasing CPX-POM dose. 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 70 of 80 
 
Protocol: CPX-POM-001 
--- DELIVERY TYPE ---- 
Page 1 of X  
 
Listing 16.2.4-8 – Prior and Concomitant Medications 
(All Patients) 
 
CPX-POM Dose Group: 30 mg/m^2 
Center/ 
Patient 
Type of 
Medication 
Therapeutic Class 
  Preferred Term 
    Verbatim 
Start Date (Day)/ 
End Date (Day) 
Total Daily Dose 
(unit)/ 
Frequency/  
Route 
 
Reason/ 
Indication 
 
 
 
 
 
 
XXXX 
 
 
XXXXXX/ 
  XXXXX/ 
    XXXXXXXXXXX 
DDMMMYYYY (<-180)/ 
DDMMMYYYY (XXX) 
XXXXXXXX (XXX)/ 
Once/  
Inhalation 
XXXXXXXXXXXX 
 
Conc.** 
Proh. [a]  
XXXXXX/ 
  XXXXX/ 
    XXXXXXXXXXX 
--MMMYYYY/ 
Ongoing  
Other, XXXX/ 
bid/ 
Cutaneous 
XXXXXX 
 
 
 
 
 
 
XXXX 
Prior* 
 
XXXXXX/ 
  XXXXX/ 
    XXXXXXXXXXX 
--MMMYYYY/ 
DDMMMYYYY (XXX) 
200 mg/  
tid/ 
Other, XXXXX 
XXXXXXXXXXXXXXXXXX 
 
 
 
 
 
 
Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY, -- represents an unknown date 
component.  
* Prior = any medication whose end date is before the date of first dose.   
** Conc. = any medication that started before the date of first dose and stopped on (or is ongoing after) the date of first dose 
OR any medication whose start date is either the same as (or after) the date of first dose.   
[a] Proh. = Prohibited medication. 
   
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                   
Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES:  
• 
Listing to be sorted by increasing CPX-POM dose. 
• 
Use abbreviations or codes to present data if not enough space (and add appropriate abbreviations / codes in footnotes). 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 71 of 80 
 
Protocol: CPX-POM-001 
  --- DELIVERY TYPE ---- 
Page 1 of X  
 
 
 
 
Listing 16.2.5 – Drug Exposure 
(All Patients) 
 
 
Center/ 
Patient 
 
CPX-POM  
Dose group 
 
Date of  
first dose 
admnistration 
Visit of  
last dose  
admnistration 
Date of  
last dose  
admnistration 
 
Exposure 
(days) 
 
Exposure 
(mg) 
XXXX 
30 mg/m^2 
DDMMMYYYY 
C1 TRT D5 
DDMMMYYYY 
XX 
XX 
XXXX 
[D2] mg/m^2 
DDMMMYYYY 
C2 TRT D5 
DDMMMYYYY 
XX 
XX 
 
<cont.> 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY.  
The CPX-POM exposure expressed in days is defined as the number of days between the first dose taken date and the last dose 
taken date + 1 day.   
The CPX-POM exposure expressed in mg is defined as: dose per m2 x Body Surface Area x CPX-POM exposure expressed in days. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                      Filename: (Specify file name.rtf) 
 
 
PROGRAMMING NOTES:  
• 
Listing to be sorted by increasing CPX-POM dose. 
 
 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 72 of 80 
 
 
Protocol: CPX-POM-001 
 
--- DELIVERY TYPE ---- 
 
   Page 1 of X  
 
Listing 16.2.6-1 – Urine concentrations of CPX-POM and Metabolites 
(All Patients) 
 
CPX-POM Dose Group: 30 mg/m^2 
Center/ 
Patient 
Parameter 
(Unit) 
Visit 
 
Assessment Sample 
___Assessment__ 
Date      Time 
Study 
Day 
Urine 
Volume 
(mL)  
CPX-POM 
Conc. 
(ng/mL) 
CPX 
Conc. 
(ng/mL) 
CPX-G 
Conc. 
(ng/mL) 
XXXX 
CPX-POM 
(XXXX) 
C1 TRT D1 
 
Pre-Dose 
DDMMMYYYY HH:MM  
XX 
XX 
XX 
XX 
 
 
 
Post-Dose [0-12] 
DDMMMYYYY HH:MM  
XX  
XX 
XX 
XX 
 
 
 
Post-Dose [12-24] 
DDMMMYYYY HH:MM  
XX  
XX 
XX 
XX 
 
 
 
 
 
 
 
 
 
 
C1 TRT D5 
Post-Dose [0-12] 
DDMMMYYYY HH:MM XX 
XX  
XX 
XX 
XX 
  
 
 
Post-Dose [12-24] 
DDMMMYYYY HH:MM XX 
XX  
XX 
XX 
XX 
 
Conc.: Concentration. 
Study Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY, -- represents an unknown 
date component. Baseline was the last non-missing assessment prior or on the first dose date. SI units and results presented. 
ND = Not Done. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                             
Filename: (Specify file name.rtf) 
 
 
 
 
 
• 
 
 
Listing 16.2.6-2 – Plasma concentrations of CPX-POM and Metabolites 
(All Patients) 
Replicate of Listing 16.2.6-1  
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 73 of 80 
 
 
Protocol: CPX-POM-001 
 
--- DELIVERY TYPE ---- 
 
   Page 1 of X  
 
Listing 16.2.6-3 – Plasma concentrations of Biomarkers Assays 
(All Patients) 
 
CPX-POM Dose Group: 30 mg/m^2 
Center/ 
Patient 
Parameter 
(Unit) 
Visit 
 
 
Assessment 
Sample 
___Assessment__ 
Date      Time 
Study  
Day 
VEGF 
Conc. 
(pg/mL) 
Percent 
change 
from 
Baseline 
IL-6 
Conc. 
(pg/mL) 
Percent 
change 
from 
Baseline 
IL-8 
Conc. 
(pg/mL) 
Percent 
change  
from 
Baseline 
XXXX 
CPX-POM(XXXX) 
C1 TRT D1 
 
Pre-Dose 
DDMMMYYYY HH:MM  
XX 
 
XX 
 
XX 
 
 
 
C1 TRT D5 
Pre-Dose 
DDMMMYYYY HH:MM XX 
XX 
XX.X 
XX 
XX.X 
XX 
XX.X 
<repeat for Day 1 and Day 5 visits of next cycles if relevant> 
<repeat for Day 22 visit of last cycle> 
Conc.: Concentration. 
The Baseline concentrations are the concentrations obtained at Day 1 Visit of Cycle 1. 
Study Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY, -- represents an unknown 
date component. Baseline was the last non-missing assessment prior or on the first dose date. SI units and results presented. 
ND = Not Done. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                     
Filename: (Specify file name.rtf) 
 
 
 
 
PROGRAMMING NOTES:  
• 
Repeat for all doses groups. 
 
 
Listing 16.2.6-4 – PBMC Biomarkers Assays 
(All Patients) 
Replicate of Listing 16.2.6-3 
 
 
 
 
PROGRAMMING NOTES:  
• 
PBMC Biomarkers are Notch 1, surviving, cyclin D, c-Myc and Hes 1 using RT-PCR.  
• 
Repeat for all doses groups. 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 74 of 80 
 
 
 
Protocol: CPX-POM-001 
 
--- DELIVERY TYPE ---- 
 
 Page 1 of X  
 
Listing 16.2.6-5 – Urine beta-glucuronidase activity 
(All Patients) 
 
CPX-POM Dose Group: 30 mg/m^2 
Center/ 
Patient Parameter (Unit) Visit 
 
Assessment Sample 
___Assessment__ 
Date      Time 
Study 
Day 
Urine  
beta-glucuronidase  
activity (U/mL)  
XXXX 
CPX-POM (XXXX) 
C1 TRT D1 
Post-Dose [0-12] 
DDMMMYYYY HH:MM  
XX  
 
 
 
Post-Dose [12-24] 
DDMMMYYYY HH:MM  
XX  
 
 
 
 
 
 
 
 
 
 
 C1 TRT D5 
Post-Dose [0-12] 
DDMMMYYYY HH:MM XX 
XX  
  
 
 
Post-Dose [12-24] 
DDMMMYYYY HH:MM XX 
XX  
 
Study Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY, -- represents an unknown 
date component. Baseline was the last non-missing assessment prior or on the first dose date. SI units and results presented. 
ND = Not Done. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                  
Filename: (Specify file name.rtf) 
 
 
PROGRAMMING NOTES:  
• 
Repeat for all doses groups. 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 75 of 80 
 
Protocol: CPX-POM-001 
             --- DELIVERY TYPE ---- 
Page 1 of X 
 
Listing 16.2.7-1 – Adverse Events 
(All Patients) 
 
CPX-POM Dose Group: 30 mg/m^2 
Center/ 
Patient 
System Organ Class/ 
  Preferred Term/ 
    Verbatim 
Start Date (Day)/ 
End Date (Day) 
Action Taken/ 
Medication or 
Therapies Taken? 
 
Outcome/  
Severity/ 
Relationship 
SAE? 
 
 
 
 
 
XXXX 
XXXXXXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXXXXX/ 
    XXXXXXXXXXXXXXXX 
DDMMMYYYY (XXX)/ 
DDMMMYYYY (XXX) 
None/ 
No 
XXXXXXXX/  
Mild/ 
Not related 
No 
 
 
 
 
 
 
 
XXXXXXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXXXXX/ 
    XXXXXXXXXXXXXXXX 
DDMMMYYYY (XXX)/ 
Ongoing 
Dose Adjusted/ 
Yes 
Resolved/  
Moderate/  
Definitely related 
Yes 
 
 
 
 
 
 
XXXX 
XXXXXXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXXXXX/ 
    XXXXXXXXXXXXXXXX 
DDMMMYYYY (XXX)/ 
--MMMYYYY 
 
XXXXXXXX/ 
XXXXXX/ 
XXXXXXX 
No 
 
<cont.> 
 
 
 
 
 
Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY, -- represents an unknown date 
component. 
MedDRA version <version #>. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                 
Filename: (Specify file name.rtf) 
PROGRAMMING NOTES:  
• 
Repeat for the other CPX-POM doses by increasing order. 
 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 76 of 80 
 
Listing 16.2.7-2 – Serious Adverse Events 
(All Patients) 
Replicate of Listing 16.2.7-1 
 
PROGRAMMING NOTES:  
• 
Repeat for the other CPX-POM doses by increasing order. 
• 
Select all AEs where SAE = Yes. 
• 
Remove column ‘SAE’ and remove SAE from footnote. 
 
 
Listing 16.2.7-3 – Adverse Events Leading to Discontinuation 
(All Patients) 
 
Replicate of Listing 16.2.7-1 
 
PROGRAMMING NOTES:  
• 
Repeat for the other CPX-POM doses by increasing order. 
• 
Select all AEs where action taken = permanently discontinued. 
 
 
Listing 16.2.7-4 – Adverse Events Leading to Death 
(All Patients) 
 
Replicate of Listing 16.2.7-1 
 
PROGRAMMING NOTES:  
• 
Repeat for the other CPX-POM doses by increasing order. 
• 
Select all AEs where outcome = Fatal  
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 77 of 80 
 
Protocol: CPX-POM-001 
   --- DELIVERY TYPE ---- 
Page 1 of X 
 
Listing 16.2.8-1 – Patients Laboratory Profile: Hematology 
(All Patients) 
 
CPX-POM Dose Group: 30 mg/m^2 
Center/ 
Patient Visit 
___Assessment__ 
Date      Time 
Study 
Day 
Parameter 
(Unit) 
Normal  
Range 
Result  
CTCAE  
grade  
Change 
from 
Baseline 
Clinical 
Interpretation 
 
 
 
 
 
 
 
 
 
XXXX 
BAS 
DDMMMYYYY HH:MM XXX 
XXXXXXXX (XXXX) 
XXXXXX 
XX 
Grade 1 
 
Normal 
 
C1 TRT D1 
DDMMMYYYY HH:MM XXX 
XXXXXXXX (XXXX) 
XXXXXX 
XX  L/H 
Grade 2 
XXXX 
Abnormal, NCS 
 
C1 TRT D4 
DDMMMYYYY HH:MM XXX 
XXXXXXXX (XXXX) 
XXXXXX 
XX  L/H 
Grade 2 
XXXX 
Abnormal, NCS 
 
C1 TRT D10 DDMMMYYYY HH:MM XXX 
XXXXXXXX (XXXX) 
XXXXXX 
XX  L/H 
Grade 3 
XXXX 
Abnormal, CS 
 
 
 
 
 
 
 
 
 
 
<for Cycle 2 to last-1 cycle, repeat for Day 1 visit and Day 4 visit if relevant> 
<for the last cycle, repeat also for Day 22 visit and Day 28 visit> 
 
 
 
 
 
 
 
 
 
 
 
 
Study Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY, -- represents an unknown 
date component. Baseline was the last non-missing assessment prior or on the first dose date. SI units and results presented. 
L/H = low/high value based upon normal ranges. R = repeat/unscheduled assessments. CS = Clinically Significant; NCS = Not 
Clinically Significant; ND = Not Done. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                               
Filename: (Specify file name.rtf) 
 
 
PROGRAMMING NOTES:  
• 
Repeat for the other CPX-POM doses by increasing order. 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 78 of 80 
 
 
Listing 16.2.8-2 – Patients Laboratory Profile: Clinical Chemistry 
(All Patients) 
 
 
Replicate of Listing 16.2.8-1 
 
PROGRAMMING NOTES:  
• 
Listing to be sorted by increasing order. 
 
 
Listing 16.2.8-3 – Patients Laboratory Profile: Coagulation and Thyroid Panel 
(All Patients) 
 
 
Replicate of Listing 16.2.8-1 
 
PROGRAMMING NOTES:  
• 
Listing to be sorted by increasing order. 
• 
Only Day 1 of each cycle. 
 
 
Listing 16.2.8-4 – Patients Laboratory Profile: Urinalysis 
(All Patients) 
 
 
Replicate of Listing 16.2.8-1 
 
PROGRAMMING NOTES:  
• 
Listing to be sorted by increasing order. 
• 
Replace ‘Day 4’ by ‘Day 5’ for each cycle. 
 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 79 of 80 
 
Protocol: CPX-POM-001 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
Listing 16.2.8-5 – Vital Signs 
(All Patients) 
 
CPX-POM Dose Group: 30 mg/m^2 
 
Center/ 
Patient 
Visit 
___Assessment__ 
Date      Time 
Study 
Day 
Parameter (unit) 
Position 
Result 
 
Change from 
Baseline 
 
 
 
 
 
 
XXXX 
BAS 
DDMMMYYYY HH:MM 
XXX 
Pulse Rate (bpm) 
Supine 
XXX + 
 
 
 
 
 
Respiratory Rate (bpm) 
Supine 
XXX 
 
 
 
 
 
Systolic BP (mmHg)  
Supine 
XXX 
 
 
 
 
 
Diastolic BP (mmHg) 
Supine 
XXX  
 
 
 
 
 
Oxygen Saturation (mmHg) 
 
XXX 
 
 
 
 
 
Body Weight (kg) 
 
XXX.X 
 
 
 
 
 
Temperature (C) 
 
XX.X 
 
 
 
 
 
 
 
 
 
 
C1 TRT D2 
DDMMMYYYY HH:MM 
XXX 
Pulse Rate (bpm) 
Supine 
XXX + 
XX 
 
 
 
 
Respiratory Rate (bpm) 
Supine 
XXX 
XX 
 
 
 
 
Systolic BP (mmHg)  
Supine 
XXX 
XX 
 
 
 
 
Diastolic BP (mmHg) 
Supine 
XXX  
XX 
 
 
 
 
Oxygen Saturation (mmHg) 
 
XXX 
XX 
 
 
 
 
Body Weight (kg) 
 
XXX.X 
X.X 
 
 
 
 
Temperature (C) 
 
XX.X 
X.X 
 
 
 
 
 
 
 
 
<repeat for Day 3, Day 4, Day 5, Day 6 and Day 10 visits of Cycle 1> 
<for Cycle 2 to last-1 cycle, repeat from Day 1 to Day 6 visits if relevant> 
<for the last cycle, repeat also for Day 22 visit and Day 28 follow-up visit> 
 
 
 
 
 
 
 
 
 
 
Study Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY. Baseline was the last 
non-missing assessment prior or on the first dose. 
+ Results of clinical importance (see SAP). BP = Blood Pressure; bpm = beats per minute; ND = Not Done. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                    
Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES:  
• 
Repeat for all doses groups 
 
 
 


 
 
 
 
 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan 
(TFL shells):   
Version 1.0 / 02FEB2018 
 
Page 80 of 80 
 
 
Protocol: CPX-POM-001 
 
      --- DELIVERY TYPE ---- 
 
Page 1 of X 
 
Listing 16.2.8-6 – ECG Results and Interpretation 
(All Patients) 
 
CPX-POM Dose Group: 30 mg/m^2 
 
Center/ 
Patient 
Visit 
Assessment Date 
(Day) 
Parameter (unit) 
Clinician Interpretation 
Result 
Change 
from 
baseline 
 
 
 
 
 
XXXX 
BAS 
DDMMMYYYY (XXX) 
Heart Rate (bpm)  
Normal 
XXX 
 
 
 
 
PR interval (msec) 
Normal 
 
 
 
 
 
QRS duration (msec) 
Normal 
 
 
 
 
 
QT interval (msec) 
Normal 
 
 
 
 
 
QTcB interval (msec) 
Normal 
 
 
 
 
 
QTcF interval (msec) 
Normal 
 
 
 
 
C1 TRT D5 DDMMMYYYY (XXX) 
Heart Rate (bpm)  
Abnormal, Clinical Significant 
XXX ++ 
XX * 
 
 
 
PR interval (msec) 
Normal 
 
 
 
 
 
QRS duration (msec) 
Normal 
 
 
 
 
 
QT interval (msec) 
Normal 
 
 
 
 
 
QTcB interval (msec) 
Abnormal, Not Clinical Significant 
XXX + 
 
 
 
 
QTcF interval (msec) 
Abnormal, Not Clinical Significant 
XXX + 
 
 
<for Cycle 2 to last-1 cycle, repeat for Day 1 visit if relevant> 
<for the last cycle, repeat also for Day 28 follow-up visit> 
 
 
 
 
Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY. Baseline was the last non-
missing assessment prior or on the first dose date. 
QTcB and QTcF: +: >450 msec; ++: > 480 msec; +++: >500 msec; *: > 30 msec above baseline; **: > 60 msec above baseline.  
R = repeated/ unscheduled assessment. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                 
Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES:  
• 
Repeat for all dose groups.