Conditions: Hypogonadism
Allocation: NON_RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 18
Healthy volunteers: no

Brief summary:
A Phase 2, open-label, randomized, cross-over, pharmacokinetic study designed to determine the effect of meals of various amounts of fat given immediately prior to dosing on the pharmacokinetics of oral testosterone undecanoate. Approximately 20 hypogonadal subjects will be dosed for a 14 day run-in period. This will be followed by a randomized sequence of five periods over a 6 day confinement period. Subjects will receive a randomly ordered sequence of breakfast meals containing various amounts of fat, fasting, 15 g, 30 g, 45 g and a high fat breakfast consistent Guidance for Industry on Food-Effect Bioavailability and Fed Bioequivalence Studies.

Detailed description:
This is a Phase 2, open-label, randomized, cross over, pharmacokinetic study. Subjects will initially be dosed for 2 weeks (Run-In Phase) to allow suppression of endogenous testosterone production, while allowing the oral TU to reach steady state. The subjects will then be confined to a clinical unit in which they undergo the PK Phase of the study. During the PK Phase of the study, subjects will undergo a five-period cross-over in which oral TU is dosed twice daily. Subjects will dose in the morning and in the evening immediately prior to protocol-defined meals. The protocol-defined breakfasts will contain various levels of fat including 15 g, 30 g, 45 g, a breakfast consistent with the fat and calorie content of the high-fat breakfast consistent with recommendations in the Guidance for Industry on Food-Effect Bioavailability and Fed Bioequivalence Studies (December 2002), or while fasting (with no meal until 4 hours post-dose). Subjects will be randomized to a designated sequence of the protocol-defined breakfasts, or the fasted state. The subjects will be required to consume the entire breakfast within 20 minutes during the PK Phase. The protocol-defined evening meal will be required to be consumed within 20 minutes. The 5 meal periods will occur on sequential days.

Approximately twenty (20) subjects will be enrolled in order to ensure completion of 16 subjects.

Arms:
arm 1: Oral Testosterone Undecanoate 237 mg administered twice daily immediately prior to Fasting at breakfast and immediately prior to dinner. arm 2: Oral Testosterone Undecanoate 237 mg administered twice daily immediately prior to 15 g fat breakfast and immediately prior to dinner. arm 3: Oral Testosterone Undecanoate 237 mg administered twice daily immediately prior to 30 g fat breakfast and immediately prior to dinner. arm 4: Oral Testosterone Undecanoate 237 mg administered twice daily immediately prior to 45 g fat breakfast and immediately prior to dinner. arm 5: Oral Testosterone Undecanoate 237 mg administered twice daily immediately prior to high fat breakfast and immediately prior to dinner.

Interventions: intervention 1: Oral Testosterone Undecanoate
Intervention descriptions: intervention 1: All study participants received Oral TU dose of 237 mg TU twice daily before breakfast and dinner for 14 days and throughout 5 crossover periods

Protocol document:
Prot_000.pdf: 
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CLINICAL STUDY PROTOCOL 
A PHASE 2 STUDY OF THE EFFECT OF MEALS WITH VARIOUS 
AMOUNTS OF FAT GIVEN IMMEDIATELY AFTER DOSING ON 
THE PHARMACOKINETICS OF AN ORAL TESTOSTERONE 
UNDECANOATE IN HYPOGONADAL MEN 
Protocol Number: 
CLAR-16015 
IND Number 
78,104 
Investigational Product: 
Testosterone Undecanoate 
Phase: 
Phase 2 
Sponsor: 
Clarus Therapeutics, Inc. 
555 Skokie Blvd., Suite 340 
Northbrook, IL 60062 
United States 
Contract Research Organization: 
Celerion Applied Translational Medicine 
621 Rose Street  
Lincoln, Nebraska 68502 
United States 
 
Protocol Date: 
15 Sep 2016 
Protocol Version: 
Version 1.0 
 
 
 
 
CONFIDENTIAL 
This protocol may not be reproduced or communicated to a third party without the 
written permission of Clarus Therapeutics, Inc. 




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2 
STUDY INFORMATION 
PRINICPAL INVESTIGATORS 
 
Ronald S. Swerdloff, MD 
Professor of Medicine, David Geffen School of Medicine at UCLA 
Chief Division of Endocrinology, Harbor-UCLA Medical Center 
Senior Investigator, Los Angeles Biomedical Research Institute 
Division of Endocrinology and the Clinical and Translational Research Center  
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center 
1124 W. Carson Street 
Torrance, CA 90502 
 
Thomas C Marbury, MD 
Orlando Clinical Research Center 
5055 South Orange Avenue 
Orlando FL 32809 
Phone: (407) 240-7878 
Fax: (407) 240-9846 
 
LABORATORIES: 
inVentiv Health Clinique 
2500, rue Einstein 
Québec (Québec) 
G1P OA2 
and 
Endocrine and Metabolic Research Lab, Los Angeles Biomedical Research Institute 
1124 W. Carson Street 
Torrance, CA  90502 
 
 
INSTITUTIONAL REVIEW BOARD: 
Copernicus Group Institutional Review Board (CGIRB) and  
Western Institutional Review Board (WIRB) 
1019 39th Avenue SE Suite 120 
Puyallup, WA 98374-2115 
Office: (360) 252-2500 or (800) 562-4789 
Fax:  (360) 252-2498 
 
 


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3 
SYNOPSIS 


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Sponsor: Clarus Therapeutics, Inc. 
Protocol No.: 
CLAR-16015 
Study Drug Name: Testosterone Undecanoate Oral 
Capsule 
Phase of Development: Phase 2 
Active Ingredient: Testosterone Undecanoate 
Date of Protocol Synopsis: 15 September 2016 
Protocol Title:  
 
A Phase 2 Study of the Effect of Meals with Various Amounts of Fat Given Immediately After Dosing on the 
Pharmacokinetics of an Oral Testosterone Undecanoate 
Objectives:  
 
Primary Objective: 
 
The objective of the study is to determine the effect of meals (breakfast) containing various amounts of 
fat on the pharmacokinetics of Clarus's formulation of oral TU at a dose of 237 mg TU (the highest 
strength capsule being developed by Clarus).   
Safety Objective: 
 
To characterize the safety and tolerability of oral TU when consumed with various meals. 
Study Sites:  Two centers in the United States 
Study Population:  
Hypogonadal men aged 18 to 65 years (inclusive), and legally able to give informed consent, as applicable by 
law. 
Number of Subjects: 
 
Approximately 20 subjects. 
Methodology: 
This is a Phase 2, open-label, randomized, cross over, pharmacokinetic study.  Subjects will initially be dosed 
for 2 weeks (Run-In Phase) to allow suppression of endogenous testosterone production, while allowing the oral 
TU to reach steady state.  The subjects will then be confined to a clinical unit in which they undergo the PK 
Phase of the study.  During the PK Phase of the study, subjects will undergo a five-period cross-over in which 
oral TU is dosed twice daily.  Subjects will dose in the morning and in the evening immediately prior to 
protocol-defined meals.  The protocol-defined breakfasts will contain various levels of fat including 15 g, 30 g, 
45 g, a breakfast consistent with the fat and calorie content of the high-fat breakfast consistent with 
recommendations in the Guidance for Industry on Food-Effect Bioavailability and Fed Bioequivalence Studies 
(December 2002), or while fasting (with no meal until 4 hours post-dose).  Subjects will be randomized to a 
designated sequence of the protocol-defined breakfasts, or the fasted state.  The subjects will be required to 
consume the entire breakfast within 20 minutes during the PK Phase.  The protocol-defined evening meal will 
be required to be consumed within 20 minutes.  The 5 meal periods will occur on sequential days. 
Approximately twenty (20) subjects will be enrolled in order to ensure completion of 16 subjects.  


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Main Criteria for Inclusion/Exclusion  
Main Inclusion Criteria 
The main inclusion criteria include: 
 
Subject must be a man 18 to 65 years of age, inclusive and legally able to give informed consent, as 
applicable by law, with a clinical diagnosis of hypogonadism (signs/symptoms consistent with 
hypogonadism for testosterone naïve subjects and history of signs/symptoms for subjects who have 
received prior treatment) and 2 morning total T values of <300 ng/dL (between 6:00 and 10:00 AM drawn 
on 2 separate days [approximately 7±2 days apart]).   
 
Subject must have adequate venous access in the left or right arm to allow collection of a number of blood 
samples via a venous cannula. 
 
Subject must be naïve to androgen-replacement therapy or washed out of prior androgen replacement 
therapies (wash out durations specified in exclusion criterion 1); that is, be willing to cease current T 
treatment, or currently not be taking T treatment.  
 
Subject on replacement therapy for hypopituitarism or multiple endocrine deficiencies must be on stable 
doses of thyroid hormone and adrenal replacement hormones for at least 14 days before Screen 1.  
 
Subject must be willing to eat entire protocol defined breakfasts and dinners. 
 
Main Exclusion Criteria 
Subject will be excluded if 1 or more of the main exclusion is applicable: 
 
Received oral topical (eg, gel or patch), intranasal, or buccal T therapy within the previous 2 weeks, 
intramuscular T injection of short-acting duration (eg, T enanthate, T cypionate) within the previous 
4 weeks, intramuscular T injection of long-acting duration (eg, AVEED®) within the previous 20 weeks, or 
T implantable pellets (Testopel®) within the previous 6 months. 
 
Has an intercurrent disease deemed clinically significant in the opinion of the investigator of any type; in 
particular, liver, kidney, uncontrolled or poorly controlled heart disease, including hypertension, congestive 
heart failure or coronary heart disease, or psychiatric-illness, including severe depression.  
 
Has had a recent (within 2 years) history of stroke, transient ischemic attack, or acute coronary event. 
 
Has had a recent (within 2 years) history of angina or stent (coronary or carotid) placement. 
 
Has a mean of the triplicate assessments of systolic BP (sBP) > 150 mm Hg and/or diastolic BP (dBP) > 90 
mm Hg at screening (if prescribed antihypertensives, subject should be taking medications on the day of the 
screening visit with a sip of water).  Subjects < 60 years of age and prescribed antihypertensives will be 
excluded if the mean of the triplicate assessment of sBP > 140 mm Hg and/or dBP > 90 mm Hg at 
screening.  
 
If receiving antihypertensive medications, has been on a stable dose for < 3 months.  
 
Has an abnormal prostate DRE (palpable nodules), elevated PSA (serum PSA > 4.0 ng/mL), International 
Prostate Symptom Score (I-PSS) > 19 points at screening, and/or history of, or current or suspected, 
prostate cancer. 
 
Has a history of, or current or suspected breast cancer. 
 
Current use of the following groups of drugs that affect T levels, T metabolism or levels of T metabolites, 
namely antiandrogens, 5 alpha reductase inhibitors (eg, dutasteride, finasteride), estrogens, long-acting 
opioid analgesics (eg, methadone hydrochloride, buprenorphine hydrochloride) or human growth hormone 
(HGH).  
Investigational Product: Testosterone Undecanoate Oral Capsule 
Doses: During the Run In phase, the dose will be 237 mg TU BID (approximately 12 hours apart) with breakfast 
and dinner meals.  During the PK Phase, the dose will be 237 mg BID immediately prior to the protocol defined 
breakfast (or fasting) and protocol defined dinner. The 237 mg dose is a soft-gel capsule which is the largest 
dose strength being developed. 
Administration Route: Oral 


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Duration of Study Participation: 
Each subject will participate in the study for approximately 8 weeks, including up to a 28-day Screening Phase, 
a 14-day out-patient Run-In Phase, and a 6-day in-patient PK Phase, followed by a 5 to 7 day Safety Follow–up 
Phase to assess safety. 
Endpoints: 
Pharmacokinetic Endpoint: 
The testosterone pharmacokinetics associated with each breakfast diet (fasting, 15 g fat, 30 g fat, 45 g fat and a 
high  fat meal) will be evaluated using non-compartmental pharmacokinetic analysis.  The parameters Cmax, 
Tmax, AUC12 and Cavg will be derived using the assay results for total T.  The concentrations and 
pharmacokinetic parameters for the individuals will be listed, along with descriptive statistics. As the treatment 
doses will be administered while endogenous T production has been suppressed, the total T values will not be 
corrected for baseline T concentrations.  Comparisons will be made between the Cmax and AUC12 and Cavg 
values obtained for each treatment, after log transformations. The 30 g fat breakfast treatment (“normal” fat 
content for the US population) will serve as the reference treatment in the comparisons to identify the effects of 
the different meals on the relative bioavailability of T.  
Safety Endpoints: 
Treatment emergent adverse events 
Pharmacokinetic Variables:  
Pharmacokinetic variables to be calculated include total T Cmax, time to maximum concentration (Tmax), area 
under the plasma concentration time-curve over the post-breakfast dosing interval (AUC12) and Cavg over the 
dosing interval. 
Safety Variables: 
Safety variables include: adverse events, routine vital sign measurements (including cuff measured sBP and 
dBP), physical examination findings, clinical laboratory tests. 
Statistical Methods: 
For all subjects enrolled in the study, descriptive tabular and/or graphical summarizations will be generated, if 
applicable. Continuous variables will be presented using descriptive statistics: number of observations (n), 
mean, standard deviation, standard error of the mean, median, and minimum and maximum values. Categorical 
values will be summarized with counts and percentages.  
All collected data will be presented in listings 
Pharmacokinetics 
Pharmacokinetic parameters will be summarized for each meal treatment. Non-compartmental analysis of the 
total T concentrations measured on the treatment days will be used to calculate PK parameters, including Cmax, 
Tmax, AUC and Cavg for each breakfast diet option. Actual sample collection times will be used for PK parameter 
determinations; summary listings and tables will be organized by nominal (scheduled) sample collection time.  
Safety 
Adverse events will be summarized and tabulated by system organ class and preferred term.  
Physical examination and results will be summarized.  
Observed values and changes from baseline in vital sign measurements, including sBP, dBP, heart rate (HR), 
will be summarized.  
Observed values and changes from baseline in laboratory test results will be summarized. Laboratory tests will 
be performed at screening and following the Day 5 24 hour PK sample. 
Date of Protocol: 15 September 2016 


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4 
TABLE OF CONTENTS 
1 
Protocol Approval Signatures .......................................................................................... 2 
2 
Study Information ............................................................................................................. 3 
3 
Synopsis .............................................................................................................................. 4 
4 
Table of Contents ............................................................................................................... 8 
5 
List of Abbreviations ....................................................................................................... 11 
6 
Introduction ...................................................................................................................... 13 
7 
Study Objectives .............................................................................................................. 18 
7.1 
Primary Objective ........................................................................................................... 18 
7.2 
Safety Objective ............................................................................................................... 18 
8 
Investigational Plan ......................................................................................................... 18 
8.1 
Overall Study Design and Plan: Description ................................................................. 18 
8.2 
Discussion of Study Design ............................................................................................. 20 
8.2.1 
Anticipated Benefits ......................................................................................... 20 
8.2.2 
Anticipated Risks .............................................................................................. 20 
8.2.3 
Dose Rationale .................................................................................................. 22 
8.3 
Selection of Study Population ......................................................................................... 22 
8.3.1 
Inclusion Criteria .............................................................................................. 22 
8.3.2 
Exclusion Criteria ............................................................................................. 22 
8.3.3 
Number of Planned Subjects ............................................................................ 24 
8.3.4 
Subject Discontinuation From Therapy or Assessments .................................. 25 
8.3.4.1 
Withdrawal Procedures ..................................................................................... 25 
8.4 
Investigational Product – Oral Testosterone Undecanoate ......................................... 26 
8.4.1 
Investigational Product Administered .............................................................. 26 
8.4.2 
Identity of Investigational Product ................................................................... 26 
8.4.3 
Investigational Product Storage and Disposal .................................................. 26 
8.4.4 
Packaging and Labeling .................................................................................... 27 
8.4.5 
Study Drug Dosing During Run-In Phase and PK Phase ................................. 27 
8.4.6 
Blinding and Randomization ............................................................................ 28 
8.4.7 
Prior and Concomitant Therapy ........................................................................ 28 
8.4.7.1 
Prohibited Medication/Therapy ........................................................................ 28 
8.4.7.2 
Other Restrictions ............................................................................................. 29 
8.4.8 
Treatment Compliance ...................................................................................... 29 
9 
Timing of Study Procedures ........................................................................................... 30 


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9.1 
Screening Phase ............................................................................................................... 30 
9.1.1 
Screen 1 Day -28 to -7 ...................................................................................... 30 
9.1.2 
Screen 2 approximately 7 (±2) days post Screen 1 ........................................... 31 
9.2 
Run-In and PK Phases .................................................................................................... 31 
9.2.1 
Run-In Phase (14±2 Days) ................................................................................ 31 
9.2.2 
Run-In Phase Dosing Day 1 ............................................................................. 32 
9.2.3 
Run-In Phase, Dosing Day 14 (±2) ................................................................... 32 
9.2.4 
PK Phase/Periods 1, 2, 3, 4, and 5 .................................................................... 33 
9.2.5 
PK Phase on Day 6 (Discharge from Unit) ...................................................... 34 
9.2.6 
Safety Follow-up Phase (5 to 7 days post last-dose) ........................................ 34 
9.3 
Early Withdrawal Visit ................................................................................................... 34 
9.4 
PK Phase Meals ................................................................................................................ 35 
9.5 
Duration of Subject Participation .................................................................................. 35 
10 
Pharmacokinetics and Safety Variables ........................................................................ 36 
10.1  Pharmacokinetic Variables ............................................................................................. 36 
10.2  Safety Variables ............................................................................................................... 37 
10.2.1 
Adverse Events ................................................................................................. 37 
10.2.1.1  Adverse Event Definition ................................................................................. 37 
10.2.1.2  Assessment of Severity ..................................................................................... 37 
10.2.1.3  Assessment of Causality ................................................................................... 38 
10.2.1.4  Action Taken .................................................................................................... 38 
10.2.1.5  Follow-up of Adverse Events ........................................................................... 38 
10.2.1.6  Documentation and Reporting of Adverse Events ........................................... 39 
10.2.2 
Serious Adverse Events (SAE) ......................................................................... 39 
10.2.2.1  Serious Adverse Event Definition .................................................................... 39 
10.2.2.2  Reporting of Serious Adverse Events ............................................................... 40 
10.2.3 
Clinical Laboratory ........................................................................................... 41 
10.2.3.1  Hematology, Chemistry, and Urine Dipstick ................................................... 41 
10.2.3.2  Prostate-Specific Antigen ................................................................................. 42 
10.2.4 
Vital Sign Measurements .................................................................................. 42 
10.2.5 
Physical Examination ....................................................................................... 43 
10.2.6 
International Prostate Symptom Score (I-PSS) ................................................ 43 
10.3  Handling and Processing of PK Blood Sample Collections ......................................... 43 
10.4  Appropriateness of Measurements ................................................................................ 44 
11 
Statistical Methods ........................................................................................................... 45 
11.1  Statistical and Analytical Plans ...................................................................................... 45 
11.2  Pharmacokinetic Endpoints ............................................................................................ 45 
11.3  Safety Endpoints .............................................................................................................. 46 


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11.3.1 
Systolic Blood Pressure .................................................................................... 46 
11.3.2 
Other Safety Endpoints ..................................................................................... 46 
11.4  Other Variables ................................................................................................................ 47 
11.4.1 
Demographic and Other Baseline Characteristics ............................................ 47 
11.4.2 
Study Drug Exposure and Compliance ............................................................. 47 
11.4.3 
Medical and Medication History ...................................................................... 47 
11.4.4 
Prior and Concomitant Medications ................................................................. 47 
11.5  Handling of Missing Data ............................................................................................... 47 
11.6  Sample Size ....................................................................................................................... 48 
11.7  Protocol Deviations .......................................................................................................... 48 
12 
Quality Assurance and Quality Control ........................................................................ 49 
12.1  Audit and Inspection ....................................................................................................... 49 
12.2  Monitoring ........................................................................................................................ 49 
12.3  Data Management and Coding ....................................................................................... 49 
13 
Records and Supplies ...................................................................................................... 50 
13.1  Drug Accountability ........................................................................................................ 50 
14 
Ethics ................................................................................................................................. 51 
14.1  Institutional Review Board ............................................................................................. 51 
14.2  Regulatory Authorities .................................................................................................... 51 
14.3  Ethical Conduct of the Study .......................................................................................... 51 
14.4  Informed Consent ............................................................................................................ 51 
14.5  Subject Confidentiality .................................................................................................... 52 
15 
Reporting and Publication, Including Archiving ......................................................... 53 
16 
References ......................................................................................................................... 54 
Appendix A. 
Schedule of Assessments ................................................................................. 55 
 
58 
Appendix B. 
Investigator Signature Page ........................................................................... 59 
Appendix C. 
International Prostate Symptom Score (I-PSS) ........................................... 60 
Appendix D. 
Protocol Defined Meals .................................................................................. 62 
 


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5 
LIST OF ABBREVIATIONS 
 
AE 
adverse event 
ALT 
alanine aminotransferase 
ANOVA 
Analysis of variance 
AST 
aspartate aminotransferase 
AUC 
area under plasma concentration-time curve 
AUC12 
area under the plasma concentration-time curve over the 12-hour 
dosing interval 
AUC24 
area under the plasma concentration-time curve over the 24-hour 
dosing interval following the AM dose 
BID 
twice daily 
BLQ 
below the limit of quantitation 
BMI 
body mass index 
BP 
blood pressure 
Cavg 
average concentration 
CI 
confidence interval 
Cmax 
maximum concentration 
Cmax1 
Cmax values associated with oral TU morning dose 
Cmax2 
Cmax values associated with oral TU evening dose 
CRF 
case report form 
CV 
cardiovascular 
dBP 
diastolic blood pressure 
DHT 
dihydrotestosterone 
DRE 
digital rectal examination 
E2 
estradiol 
eCRF 
electronic case report form 
EDTA 
Ethylenediaminetetraacetic acid 
FDA 
Food and Drug Administration 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
HCT 
hematocrit 
HDL 
high-density lipoprotein 
HR 
heart rate 
ICF 
informed consent form 
ICH 
International Conference on Harmonization of Technical Requirements for 
Registration of Pharmaceuticals for Human Use
I-PSS 
International Prostate Symptom Score 
IRB 
institutional review board 
ITT 
intent-to-treat 
LH 
luteinizing hormone
LLOQ 
lower limit of quantitation 
LS 
least square 
MedDRA 
Medical Dictionary for Regulatory Activities 
mm Hg 
millimeters of mercury 


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NaF 
sodium fluoride 
PDQ 
Psychosexual Daily Questionnaire 
PK 
pharmacokinetic(s) 
PSA 
prostate-specific antigen 
SAE 
serious adverse event 
sBP 
systolic blood pressure 
SHBG 
sex-hormone binding globulin 
SOC 
system organ class 
T 
testosterone 
TEAE 
treatment-emergent adverse event 
Tmax 
time to maximum concentration 
TRT 
testosterone replacement therapy 
TU 
testosterone undecanoate 
ULN 
upper limits of normal 
WHO 
World Health Organization 
 
 


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6 
INTRODUCTION 
The Endocrine Society defines hypogonadism as a clinical syndrome that results from failure of 
the testes to produce physiological levels of testosterone (T) (androgen deficiency) and a normal 
number of spermatozoa because of disruption of 1 or more levels of hypothalamic pituitary-
testicular axis.2 Hypogonadism may result from a genetic abnormality or may occur secondary to a 
chronic disease or from certain drug therapies. Clinical findings in adult men with the androgen 
deficiency component of hypogonadism are non-specific. The signs and symptoms suggestive of 
androgen deficiency include reduced sexual desire (libido); decreased spontaneous erections; 
breast discomfort and/or gynecomastia; low bone mineral density; dysthymia; decreased energy 
and/or motivation; reduced muscle bulk; and increased body fat. 
Testosterone is an endogenous androgen that is produced in men by Leydig cells under the 
influence of luteinizing hormone (LH) secreted by the pituitary gland. In normal men, the average 
daily production of T is approximately 7 mg. Testosterone in circulation is primarily bound to sex-
hormone binding globulin (SHBG) and albumin. Equilibrium exists between bound and unbound T 
such that only 1 to 3% of the total circulating T is free. Total T levels (serum or plasma) typically 
range between 300 and 1000 ng/dL in eugonadal men.3 
Testosterone, in addition to being directly responsible for certain actions, serves as a precursor to 2 
active metabolites, namely, dihydrotestosterone (DHT) and estradiol (E2). Dihydrotestosterone is 
formed by the intracellular action of 5-reductase on T within target tissues (eg, muscle, prostate). 
Testosterone and DHT exert their pharmacological activity in androgen-sensitive target tissue by 
binding with the androgen receptor. At physiologic levels, the action of T and DHT differs. 
Although both androgens bind to the same receptor, the T-receptor complex regulates 
gonadotropin secretion and is responsible for Wolffian duct stimulation during sexual 
development. In contrast, the DHT-receptor complex is responsible for external virilization during 
fetal development and DHT is the primary androgen responsible for sexual maturation and adult 
male sexual activity. Which androgen is responsible for the control of spermatogenesis is poorly 
understood.4 
Testosterone deficiency is characterized by abnormally low levels of circulating T. There are a 
variety of causes of male hypogonadism but essentially all of these fall into 1 of 2 categories: 
primary hypogonadism (resulting from a defect of androgen production/secretion at the testicular 
level) and secondary hypogonadism (resulting from a defect in gonadotropin production/secretion 
at the hypothalamic-pituitary level). In primary hypogonadism, gonadotropin (ie, LH and follicle-
stimulating hormone [FSH]) levels are abnormally high because the negative feedback action of T 
to suppress secretion is absent. Conversely, secondary hypogonadism is associated with low 
gonadotropin levels. Some hypogonadal states may involve a defect at more than 1 physiological 


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level. Regardless of the cause, adult male hypogonadism is generally associated with a 
constellation of symptoms, often composed of diminished libido, depressed mood, decreased 
muscle strength, increased fat mass and reduced energy. Testosterone deficiency is also a risk 
factor for osteoporosis and has recently been implicated as a potential risk factor in coronary artery 
disease.5,6 
The goal of T replacement therapy (TRT) is to restore T levels to the eugonadal range and thereby 
restore normal male secondary sexual characteristics and behavior and to mimic the somatic action 
of T (eg, hemoglobin, muscle mass, nitrogen balance, bone mineral density). Several 
pharmacologic preparations of T (or active derivatives or pro-drugs) have been developed and 
approved for androgen-replacement therapy. These products can be divided into 5 main categories: 
oral androgens (eg, methyltestosterone, T undecanoate [TU; not currently available in the United 
States]); intramuscular T-esters (eg, T-enanthate, T-cypionate, TU); transdermal T preparations 
(T-gels, T-solutions, and non-scrotal T-patches); a buccal T delivery system; and an intranasal T 
delivery system. 
The use of oral TU for TRT is not new. A non-self-emulsifying drug delivery system oral TU 
formulation containing 40 mg of TU dissolved in oleic acid is approved and has been available for 
use for decades in over 80 countries around the world (including Canada and most countries in 
Europe) but not in the United Stated. Following administration, the oral TU dose undergoes 
entero-lymphatic absorption from the gut, bypassing the portal circulation and thereby 
circumventing first-pass hepatic metabolism. The pharmacokinetic (PK) profile of this TU 
formulation is highly variable and, consequently, this TU formulation has generally not been 
regarded as optimal for the treatment of male hypogonadism.7 
Clarus Therapeutics, Inc. (Clarus) is developing a unique oral TU formulation for TRT in 
hypogonadal men. Testosterone undecanoate (TU) is an extremely lipophilic T-ester, much more 
lipophilic than T, and thus is recognized by the small intestine as a fat. Accordingly, most of an 
orally absorbed TU dose is absorbed via the intestinal lymphatics thus avoiding first-pass hepatic 
metabolism. Clarus’s TU is formulated in a lipid matrix that contains other lipophilic substances 
and an emulsifier and is administered in a soft-gel capsule. All the excipients in the TU 
formulation are commonly used in the pharmaceutical and/or food industry and pose no known 
health risks. This orally administered TU formulation constitutes a self-emulsifying drug delivery 
system designed to promote the solubility, absorption, and subsequent bioavailability of TU. Once 
absorbed, non-specific esterases cleave the fatty acid chain to yield T that provides the androgenic 
activity of this formulation.  
Clarus has evaluated its oral TU formulation in 5 Phase 2 studies and 2 Phase 3 studies. In repeat-
dose Phase 2 studies, the serum concentrations of T, DHT, and E2 reached steady-state by the 


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seventh day of dosing.  In a single-dose, 5-period study of the effect of food with various levels of 
fat, in which the meal was consumed before dosing, demonstrated that the formulation can be 
taken across the spectrum of low-normal-high fat meals but bioavailability was substantially 
reduced when the formulation was taken in the fasted state. Increasing fat in the diet increases the 
bioavailability of T, with a high-fat meal (50% of calories of the approximately 1000 calorie meal 
as fat) resulting in about a 31% higher exposure compared to a standard (30% fat) meal. The 
formulation should not be taken in a fasted state, since fasting results in about a 40% reduction in 
absorption compared with a meal that has 30% of its calories as fat.  In that study, a high dose of 
oral TU, 474 mg, was evaluated.  
Another phase 2 open-label, single oral TU dose study was conducted in eight (8) hypogonadal 
men at a single study site.  Each participant received a single oral TU dose of 316 mg TU (two 158 
mg TU capsules) immediately prior to a standardized breakfast meal comprised of 25 to 30 % of 
calories as fat.  Subjects were asked to consume the entire breakfast meal in no more than 30 
minutes. Blood samples were collected into four different types of tubes, Plain, with no additives, 
NaF +EDTA, NaF + Oxalate, and NaF containing tubes at pre-dose, and hourly for 12 hours post-
dose. This study was performed, in part, to confirm and expand the findings published by 
Lachance et al7.  which demonstrated that when oral TU is administered to hypogonadal men, 
conversion of TU to T continues after blood collection unless the action of non-specific esterases is 
inhibited at the time blood is drawn for measurement of T.  Preliminary review of the data indicate 
an increased conversion of TU to T at every post dose time point for results collected in plain tubes 
as compared to those tubes containing an esterase inhibitor (tubes containing sodium fluoride). 
Final analyses of this study are not yet available. 
In Phase 3, the formulation was initially evaluated in a 12-month, randomized, active-controlled, 
dose-titration study (CLAR-09007; N=325). The study initiated subjects on oral TU at 316 mg TU 
twice daily (BID) after meals. The meals at PK visits approximated the average fat content of the 
American male diet with about 30 g of fat.  Unlike a food effect study, the subjects were not 
required to consume the whole meal. Only those subjects requiring dose titration on Day 30, based 
on a single time point (4 to 6 hours after dose) serum T determination, had an opportunity for a 
second titration on Day 60. Subjects who did not require dose titration at Day 30 continued on the 
316 mg TU BID dose to Day 90, without additional assessments of serum T levels. On Day 90, 
87.2% of subjects on oral TU achieved a serum T average concentration (Cavg) in the eugonadal 
range (ie, 300 to 1000 ng/dL), meeting the primary efficacy endpoint of the study; however, 
roughly one-quarter of subjects on oral TU had serum T maximum concentrations (Cmax) that fell 
outside the targets for Cmax set by the Food and Drug Association (FDA). Approximately 14% of 
subjects had a Cmax >2500 ng/dL and 13% had a Cmax of 1800 to 2500 ng/dL. The safety profile of 
the oral TU group was similar to that of the active comparator group (AndroGel® 1%). In Study 


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CLAR-09007, the incidence of any adverse event (AE), any serious AE (SAE), and any AE 
leading to discontinuation of study drug for oral TU-treated patients was 68.3%, 6.8%, and 5.0%, 
respectively, as compared with 62.5%, 3.8%, and 3.1% in patients who received AndroGel. Some 
of the differences in the AE profile, such as the incidence of edema, and an increase in mean Day 
90 baseline systolic blood pressure (sBP)/diastolic blood pressure (dBP) of 2.6/2 mm Hg may have 
been related to the higher T exposure in the subjects who received oral TU, with the Day 90 serum 
T Cavg (standard deviation) in the oral TU group of 628 (343) ng/dL compared with 485 (220) 
ng/dL in the AndroGel group. 
The results of CLAR-09007 study led Clarus to develop a revised dose-titration algorithm and test 
it in a second Phase 3 trial. This trial (CLAR-12011) was a single-arm, 114-day dose-titration 
study. Like CLAR-09007, subjects were initiated on oral TU at a dose of 316 mg TU BID, but in 
this trial all subjects had 2 opportunities to undergo dose titration.  Subjects in CLAR-12011 took 
their dose within 15 minutes of consuming meals. Subjects were provided with meal options which 
were similar to that used in the previous Phase 3 trial.  Titration decisions were based on a serum T 
concentration drawn 3 to 5 hours post-dose, and the T concentration upon which dose reduction 
occurred was lower than that used in CLAR-09007 study. On Day 114, 75.0% of subjects on oral 
TU achieved a T Cavg in the eugonadal range (ie, 300 to 1000 ng/dL), meeting the primary efficacy 
endpoint of the study. The frequency of high Cmax values was substantially decreased. 
Approximately 3% of subjects had a Cmax > 2500 ng/dL and 6% had a Cmax of 1800 to 2500 ng/dL. 
The FDA has set targets for T Cmax > 2500 ng/dL at 0% of subjects and 5% of subjects with a T 
Cmax of 1800 to 2500 ng/dL. The incidence of any AE, any SAE, and any AE leading to 
discontinuation of study drug was 48.6%, 1.4%, and 2.1%, respectively. No AE could be directly 
associated with an elevated T Cmax. The mean change in baseline sBP/dBP at Day 114 was 
0.1/0.5 mm Hg, which was less than seen in the previous study and may reflect the lower mean T 
Cavg 422 ng/dL (standard deviation 171) in study CLAR-12011. Approximately 75% of 
CLAR-12011 subjects had a final dose that was lower than the starting dose; therefore, a lower 
starting dose was studied in the next Phase 3 study, CLAR-15012. 
Currently ongoing, CLAR-15012 is a multicenter, Phase 3, randomized, open-label, active-
comparator group, efficacy (based on Cavg of T), and safety study in adult hypogonadal male 
subjects. Enrollment into the study is based on selection criteria designed to be the general 
population of hypogonadal men. Subject’s study drug dose is determined by a dose-titration 
algorithm that bases dose-titration decisions on total T Cavg. Subjects may be naïve to androgen 
replacement therapy or washed out of prior androgen replacement therapies. A total of about 550 
subjects were screened in order to enroll 222 subjects, which meets both scientific and regulatory 
objectives. Subjects who meet all eligibility criteria were randomly assigned in a 3:1 ratio such that 
166 subjects were assigned to the oral TU treatment arm and 56 subjects were assigned to receive 


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Axiron, an active comparator which is a prescribed topical T replacement product.  Treatment lasts 
approximately 3.5 months, including up to a 21 day Screening Phase (Screen 1, Screen 2, and 
Screen 3 visits), a 70-day Titration Phase, a 35 day Maintenance Phase, and an end-of-study visit, 
Visit 7 Day 105 (± 3 days).  As the study is ongoing, results are not yet available. 
The Investigator’s Brochure presents a full discussion of the pre-clinical toxicology, metabolism, 
pharmacology, and results in humans.9 


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7 
STUDY OBJECTIVES 
7.1 
Primary Objective 
To determine the effect of meals (breakfast) containing various amounts of fat on the 
pharmacokinetics of Clarus's formulation of oral TU at a dose of 237 mg TU (the highest strength 
capsule being developed by Clarus).   
7.2 
Safety Objective 
To characterize the safety and tolerability of oral TU when consumed immediately before various 
meals. 
8 
INVESTIGATIONAL PLAN 
8.1 
Overall Study Design and Plan: Description 
This will be a multicenter, Phase 2, repeated, twice daily dose, food effect study in which subjects 
are randomized to a sequence of meals that vary primarily in fat content.  Approximately 20 
hypogonadal subjects will be enrolled in order to complete approximately 16 subjects.  Subjects 
may be naïve to androgen replacement therapy or washed out of prior androgen replacement 
therapies as detailed in exclusion criteria. 
There will be a Run-In Phase (twice daily dosing with meals) designed to suppress subjects’ 
endogenous testosterone production while allowing the oral TU to reach steady state followed by a 
PK Phase.  Throughout the study, the dose of study drug will be 237 mg TU twice daily, which is 
the highest strength formulation in development and the starting dose for the ongoing Phase 3 
study, CLAR-15012.  
After the 14 day Run-In Phase, subjects will be confined in the clinic for approximately 6 
consecutive days for evaluations and serial blood draws in the PK Phase.  Subjects will present at 
the clinic on the evening of Day 14 prior to dinner time and will be dosed with oral TU 
immediately prior to a dinner meal.  They will remain in the clinic until collection of 24-hour serial 
sampling following morning dosing in Period 5 of the PK Phase. On each of the PK Phase Periods 
1 through 5, the subject will be dosed immediately prior to the breakfast meal (or in the AM with 
240 mL of water for the fasting period).  The breakfasts will be defined and contain approximately 
850 calories with 15 g fat, 30 g fat, or 45 g fat and those meals suggested in the Guidance for 
Industry on Food-Effect Bioavailability and Fed Bioequivalence Studies (December 2002), namely 
after an overnight fast or with a high-calorie and high-fat meal (approximately 1000 calories and 
50% of the calories from fat).  The 15 g, 30 g, and 45 g fat meals are meal options that are 
incorporated into the ongoing Phase 3 study. Subjects will be randomized to a sequence of the five 


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defined meal plans (including fasting) to be administered on PK Phase Periods 1 through 5 (Days 1 
through 5).   
Meal plans provided during PK Phase are as follows: 
Meal Plan A (Fasting) 
Overnight fast (≥10 hours)  
Dose oral TU with 240 mL of water 
Fast additional 4 hours 
Lunch 30 grams fat 
Dinner 30 grams fat 
Meal Plan B (15 gm fat) 
Overnight fast (≥10 hours) 
Dose oral TU immediately prior to breakfast 
Breakfast 15 grams fat 
Lunch 30 grams fat 
Dinner 30 grams fat 
Meal Plan C (30 gm fat, Reference Meal) 
Overnight fast (≥10 hours) 
Dose oral TU immediately prior to breakfast 
Breakfast 30 grams fat 
Lunch 30 grams fat 
Dinner 30 grams fat 
Meal Plan D (45 gm fat) 
Overnight fast (≥10 hours) 
Dose oral TU immediately prior to breakfast 
Breakfast 45 grams fat 
Lunch 30 grams fat 
Dinner 30 grams fat 
Meal Plan E (FDA high-calorie high-fat) 
Overnight fast (≥10 hours) 
Dose oral TU immediately prior to breakfast 
Breakfast FDA high-fat, high-calorie meal 
(≈1000 calories, 50% of calories as fat) 
Lunch 30 grams fat 
Dinner 30 grams fat 
 
 
The confinement for the PK Phase will begin immediately prior to the evening dose and meal on 
Run-In Day 14, and will continue through collection of a blood sample 24 hours after the morning 
dose of the fifth dosing (Period 5) for a total of approximately 135 hours. During the PK Phase, 
subjects will have all meals provided, will undergo observed dosing (dosing of study medication 
taking from site inventory will be observed by site personnel), will have blood samples collected 
and will have limited activity. During this phase, the subjects must consume their entire breakfast 
and dinner meals and study drug will be administered in the morning and evening (approximately 
12 hours apart) immediately before breakfast and dinner.  
For all subjects, serial blood samples will be collected as follows: 0 (pre-morning dose), 2, 4, 6, 9, 
12, 14, 16, 18, 21, and 24 hours after the morning dose.  Blood sample collection should be 
performed within ± 10 minutes of the scheduled time points (with the exception of the 0-hour time 


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point which should be administered no more than 5 minutes before oral TU dose administration on 
each PK Phase Period).  
Subjects will be released from the clinic following the 24-hour blood draw and designated end of 
study activities of the PK Phase, which occurs the morning after the fifth PK Phase study period. 
8.2 
Discussion of Study Design 
This will be a Phase 2 open-label, food effect study in adult hypogonadal male subjects. 
Enrollment into the study will be based on selection criteria designed to sample the general 
population of hypogonadal men. The study includes an up to 28-day Screening Phase, a 14 day 
outpatient Run-in Phase, followed by an in-patient PK Phase (6 days), and then a Follow up Phase.  
The primary objective of the study is to determine the effect of meals (breakfast) containing 
various amounts of fat on the pharmacokinetics of Clarus's formulation of oral TU at a dose of 237 
mg TU.  The period associated with the randomly assigned 30 g fat breakfast meal will be 
considered the reference period.   
8.2.1 Anticipated Benefits 
This study only requires short term exposure to testosterone, yet the management of hypogonadism 
requires chronic therapy; therefore, participants in this study will not get therapeutic benefit for 
their hypogonadism.  However, the subjects may benefit from the screening evaluation as it may 
identify health issues that require further follow up.  Chronic treatment with TRT may provide a 
wide range of benefits for men with hypogonadism, including improvement in libido and sexual 
function, increased bone density, increased muscle mass, decreased adiposity, and increased 
quality of life. The goal of TRT is to restore T levels to the eugonadal range and thereby restore 
normal male secondary sexual characteristics and behavior and to mimic the somatic action of T 
(eg, hemoglobin, muscle mass, nitrogen balance, bone mineral density). Several pharmacologic 
preparations of T (or T pro-drugs) have been developed and approved for TRT. 
8.2.2 Anticipated Risks 
This study will only require short term exposure to testosterone, so any androgen associated risk is 
expected to be minimal.  In addition, screening criteria are designed to identify subjects who are at 
high risk and exclude them from participating in the study.  Clarus’s oral TU has been dosed for up 
to 2 years in Phase 3 studies with a well-tolerated safety profile, which is comparable to that of a 
commonly prescribed topical TRT, AndroGel.  The dose used in this study is lower than the dose 
that most subjects were exposed to in the Phase 3 studies.  Both Phase 3 studies dosed subjects for 


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the first 21 days of treatment at a dose level of 316 mg BID, but this study will dose subjects for 
less than 21 days at 237 mg BID, which should add a further margin of safety. 
Androgens are contraindicated in men with carcinoma of the breast and known or suspected 
carcinoma of the prostate. In men receiving androgen-replacement therapy, surveillance for 
prostate cancer should be consistent with practices for eugonadal men. Geriatric subjects treated 
with androgens may be at an increased risk for the development of prostatic hyperplasia and 
prostatic carcinoma.  Potential study participants will be screened by history, physical exam 
including digital rectal exam and lab testing [prostate-specific antigen (PSA)], in order to identify 
subjects who are at higher risk. 
Other potential side effects with androgen therapy include gynecomastia and edema with or 
without congestive heart failure in subjects with pre-existing cardiac, renal, or hepatic disease. Oral 
therapy with high doses of 17-α –alkylated androgens (eg, methyltestosterone) has been associated 
with serious hepatic effects that can have life-threatening or fatal complications, although liver 
toxicity has not been observed following the oral administration of natural T or T esters including 
TU. 
Long-term clinical safety trials have not been conducted to assess the cardiovascular (CV) 
outcomes of TRT in men. To date, epidemiologic studies and randomized controlled trials have 
been inconclusive for determining whether or not the incidence of major adverse CV events, such 
as non-fatal myocardial infarction, non-fatal stroke, and CV death, is higher in men who use T 
compared to non-users. Some studies, but not all, have reported an increased risk of major adverse 
CV events in association with use of TRT in men. Subjects should be informed of this possible 
risk. There have been post-marketing reports of venous thromboembolic events, including deep 
vein thrombosis and pulmonary embolism, in subjects using T products. All subjects who report 
symptoms of pain, edema, warmth, and erythema in the lower extremities should be evaluated for 
deep vein thrombosis and those who present with acute shortness of breath should be evaluated for 
pulmonary infarction. If a venous thromboembolic event is suspected, treatment should be 
discontinued and appropriate workup and management initiated. 
The total volume of blood to be collected from each subject during the study will not exceed 
approximately 500 mL, the volume of a routine blood donation, with possible reduction in 
hemoglobin and hematocrit. 


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8.2.3 Dose Rationale 
Subjects enrolled in the CLAR-16015 will receive 237 mg capsules of oral TU.  The 237 mg TU 
capsule is the highest dose strength in development by Clarus.  The FDA food effect guidance 
indicates that the food effect study should investigate the highest dosage strength to be marketed. 
8.3 
Selection of Study Population 
Adult hypogonadal male subjects will be eligible for enrollment in the study based on the inclusion 
and exclusion criteria listed below.  Subjects will undergo screening procedures up to 28 days 
before the start of study drug treatment. 
8.3.1 Inclusion Criteria 
To be eligible for study entry subjects must satisfy all of the following criteria: 
1. Man 18 to 65 years of age, inclusive, with a clinical diagnosis of hypogonadism 
(signs/symptoms consistent with hypogonadism for testosterone naïve subjects and history 
of signs/symptoms for subjects who have received prior treatment) as well as testosterone 
levels consistent with hypogonadism as defined by 2 morning total T values of <300 ng/dL 
(between 6:00 and 10:00 AM drawn on 2 separate days [approximately 7 (±2) days apart]. 
2. Adequate venous access in the left or right arm to allow collection of a number of blood 
samples via a venous cannula. 
3. Must be naïve to androgen-replacement therapy or washed out of prior 
androgen-replacement therapies; that is, be willing to cease current T treatment or currently 
not be taking T treatment, (washout durations specified in exclusion criterion #1). Subjects 
must remain off all forms of T, except for dispensed study drug, throughout the entire 
study. 
4. Subjects on replacement therapy for hypopituitarism or multiple endocrine deficiencies 
must be on stable doses of thyroid hormone and adrenal replacement hormones for at least 
14 days before Screen 1. 
5. Has voluntarily given written informed consent to participate in this study. 
8.3.2 Exclusion Criteria 
Subjects will be excluded from the study if 1 or more of the following criterion is applicable: 


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1. Received oral topical (eg, gel or patch), intranasal, or buccal T therapy within the previous 
2 weeks, intramuscular T injection of short-acting duration (eg, T enanthate, T cypionate) 
within the previous 4 weeks, intramuscular T injection of long-acting duration (eg, 
AVEED) within the previous 20 weeks, or T implantable pellets (Testopel®) within the 
previous 6 months. 
2. Has an intercurrent disease deemed clinically significant in the opinion of the investigator 
of any type; in particular, liver, kidney, uncontrolled or poorly controlled heart disease, 
including hypertension, congestive heart failure or coronary heart disease, or psychiatric-
illness, including severe depression. 
3. Has had a recent (within 2 years) history of stroke, transient ischemic attack, or acute 
coronary event. 
4. Has a mean of the triplicate assessment of sBP > 150 mm Hg and/or dBP > 90 mm Hg at 
screening (if prescribed antihypertensives, subject should be taking medications on the day 
of the screening visit with a sip of water).  Subjects < 60 years of age and prescribed 
antihypertensives will be excluded if the mean of the triplicate assessment of sBP > 140 
mm Hg and/or dBP > 90 mm Hg at screening.  
 
5. Has had recent (within 2 years) history of angina or stent (coronary or carotid) placement. 
6. Has untreated, severe obstructive sleep apnea. 
7. Has clinically significant abnormal laboratory values, including serum transaminases > 2 × 
upper limits of normal (ULN), serum bilirubin > 1.5 × ULN and serum creatinine > 1.5 × 
ULN. 
8. Has a hematocrit (HCT) value of < 35% or > 48%. 
9. Has a history of polycythemia, either idiopathic or associated with TRT treatment. 
10. Is a diabetic subject with a glycosylated hemoglobin > 8.5%. 
11. Has a body mass index (BMI) ≥ 38 kg/m2. 
12. Has been on stable doses of antihypertensive medication for < 3 months. 
13. Has an abnormal prostate digital rectal examination [(DRE); palpable nodules], elevated 
PSA (serum PSA > 4.0 ng/mL), I-PSS > 19 points at screening, and/or history of, or current 
or suspected, prostate cancer. 


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14. Has a history of, or current or suspected, breast cancer. 
15. Has a history of abnormal bleeding tendencies or thrombophlebitis unrelated to 
venipuncture or intravenous cannulation within the previous 2 years. 
16. Use of dietary supplements such as saw palmetto or phytoestrogens and any dietary 
supplements that may increase total T, such as androstenedione or dehydroepiandrosterone 
within the previous 4 weeks. 
17. Has known malabsorption syndrome and/or current treatment with oral lipase inhibitors 
(eg, orlistat [Xenical®]) and/or bile acid-binding resins (eg, cholestyramine [Questran®], 
colestipol [Colestid®]) or treatments that promote gastric emptying (eg, metoclopramide 
[Reglan®]). 
18. Inability to observe all rules and smoking restrictions in place at the clinical facility during 
confinement. 
19. Has history of abuse of alcohol or any drug substance within the previous 2 years. 
20. Poor compliance or unlikely to keep clinic appointments and remain for entire confinement 
period. 
21. Has received any drug as part of another research study within 30 days of initial dose 
administration in this study. 
22. Donated blood (≥ 500 mL) within the 12-week period before the initial study dose. 
23. Current use of the following groups of drugs that effect T levels, T metabolism or levels of 
T metabolites, namely antiandrogens, 5-alpha-reductase inhibitors (eg, dutasteride, 
finasteride), estrogens, long-acting opioid analgesics (eg, methadone hydrochloride, 
buprenorphine hydrochloride) or human growth hormone (HGH). 
24. Unwilling or unable to follow the dietary requirements for this study. 
8.3.3 Number of Planned Subjects  
Two study centers in the United States will participate in the study. The plan is to enroll 
approximately 20 subjects in the study. 


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8.3.4 Subject Discontinuation From Therapy or Assessments 
Subjects may stop study drug for any of the following reasons: 
 
Subject request. 
 
Use of non-permitted concurrent therapy as assessed by the medical monitor and sponsor. 
 
Non-compliance with the study drug or study schedule. 
 
Lost to follow-up. 
 
Occurrence of AEs not compatible with the continuation of subject participation in the study, 
in the investigator’s opinion, or unacceptable to the subject to continue. 
 
Investigator request. 
 
Significant intercurrent illness. 
 
Sponsor request. 
Subjects may withdraw from the study (study drug and assessments) at any time without prejudice 
to further treatment (withdrawal of consent). Efforts should be made to determine why the subject 
is withdrawing. The subject will be asked about the reason(s) for withdrawal and the presence of 
any adverse events (AEs) and the reason(s) will be documented in the case report form 
(CRF/eCRF). 
Reasonable efforts will be made to contact subjects who are lost to follow-up. These efforts must 
be documented in the subject’s file. 
The sponsor has the right to terminate the study at any time. In this event, the investigators will be 
informed of the reason for study termination. 
8.3.4.1 Withdrawal Procedures 
Subjects may withdraw from the study at any time without prejudice to further treatment. If 
possible, the subject will be seen by an investigator and undergo the safety follow-up assessments 
and procedures (Appendix A). If the subject cannot be seen in person, phone/email/other follow-up 
should be attempted to ascertain the reason for withdrawal. Adverse events should be followed for 
7 days after the last dose of study drug, and all remaining study drug should be returned by the 
subject. 


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8.4 
Investigational Product – Oral Testosterone Undecanoate 
8.4.1 Investigational Product Administered 
Subjects in the study will receive orally administered TU 237 mg BID for 14 (±2) days during the 
Run-In Phase and throughout Days 1 through 5 of the PK Phase.  
8.4.2 Identity of Investigational Product  
Oral TU capsules are soft-gel capsules. The capsules will be manufactured in accordance with 
current Good Manufacturing Practice regulations by Catalent Pharma Solutions (St. Petersburg, 
FL). The soft-gel capsules will be manufactured with 237.46 mg TU, which will nominally be 
referred to as 237 mg TU capsules. The 237 mg TU capsules are orange opaque in color and are 
equivalent to 150 mg T per capsule. Testosterone undecanoate will be solubilized in a proprietary 
mixture of lipid excipients and emulsifiers that are generally regarded as safe and/or commonly 
used by the pharmaceutical and food industries.  
Subjects will receive 237 mg TU BID for 14 (±2) days leading up to the 6 day PK Phase.  Doses of 
TU are to be taken BID with meals (breakfast and dinner), approximately 12 hours apart. The 
capsules are to be taken immediately before the start of the meal.   
During the PK Phase, the subjects will take a single 237 mg TU capsule immediately before the 
protocol-defined breakfast and again immediately before the protocol-defined evening meal. 
Subjects should consume their entire morning and evening meals within 20 minutes.  Subjects will 
consume a standardized mid-day meal during PK Phase. Snacks may be provided to subjects only 
after the mid-day meal.  
8.4.3 Investigational Product Storage and Disposal 
The TU capsules will be packaged in a high-density polyethylene safety bottle that should be 
stored in a dry place at room temperature (25°C or 77°F). Excursions are permitted to 15°C to 
30°C (59°F to 86°F). 
Testosterone and related substances like TU are Schedule III non-narcotic, controlled substances. 
These study drugs must be stored at the site in a securely locked, substantially constructed cabinet 
or other substantially constructed enclosure with limited access to prevent theft or diversion of the 
drug into illegal channels of distribution. 
Subjects must be instructed to ensure that all study drugs be kept out of reach of children.  


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Study site Standard Operating Procedures will be followed for the disposal of the study 
formulation upon approval of the Sponsor or designee. 
8.4.4 Packaging and Labeling 
The study drug is for investigational use only and is to be used only within the context of this 
study. The study drug supplied for this study must be maintained under adequate security and 
stored under the conditions specified on the label until dispensed for subject use or returned to the 
sponsor. 
The clinical study labeling was done by Catalent Pharma Solutions, Philadelphia, PA and an over 
label specific to this study, CLAR-16015, will be applied to all investigational product prior to 
study start at each center by a Clarus representative. All packaging and labeling operations will be 
performed according to Good Manufacturing Practice for Medicinal Products and the relevant 
regulatory requirements. 
The TU soft-gel capsules are packaged in high-density polyethylene bottles (120 capsules per 
bottle). 
8.4.5 Study Drug Dosing During Run-In Phase and PK Phase 
Subjects will self-administer 237 mg oral TU BID for a 14 day Run-in Phase. Subjects will be 
asked to record their morning and evening doses every day during the Run-In Phase. The evening 
of Day 14 (±2) subjects will report to the clinic or Phase 1 unit before their PM dose and dinner to 
begin the PK Phase.  Subjects will take their PM dose on Day 14 from the same bottle that was 
dispensed on Dosing Day 1.  Following that dose, study drug will be collected and accountability 
will be performed.  Subjects will take their study dose immediately prior to the protocol-defined 
dinner meal provided.  During the entire PK Phase of the study, subjects will be confined to the 
clinic/unit and will be administered 237 mg TU immediately prior to the protocol-defined 
breakfast, and immediately prior to the protocol-defined dinner. During the PK Phase Periods 1 
through 5, site personnel will administer all study drug from site inventory. 
In the event of a missed dose during the Run-In Phase, the missed dose will be documented and the 
subject will wait until it is time to take the next dose of study drug, in keeping with the scheduled 
dosing regimen.  
During the PK Phase if the subject’s AM or PM dose is missed, he may be asked to repeat that 
study day including the assigned protocol-defined meals and serial sampling for 12 – 24 hours.   


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Per protocol, the 24 hour blood collection time point also serves as the time 0 for the next day’s 
serial sampling.  However, if the dose-associated meal is not ready to be served at the 24 hour time 
point (ie., time 0) a window of up to one hour is acceptable and the sample collection clock for that 
dose (time 0) begins with the actual time of the dose. This may require that the 24-hour sample 
from the previous dose does not serve as time 0 for the following dose. 
8.4.6 Blinding and Randomization 
This is an open-label study. Subjects will be randomly assigned to one of the five  sequences 
(shown below) of breakfast meals where the sequences follows a Latin square design for a 5 period 
cross-over study. 
1. ABCDE 
2. BCEAD 
3. CEDBA 
4. DABEC 
5. EDACB 
 
8.4.7 Prior and Concomitant Therapy 
If any medication or nutritional supplement is taken, the name, dose, route, frequency of dosing, 
and reason for use will be recorded on the concomitant medication page in the CRF/eCRF. 
Subjects will be asked about their treatment history for hypogonadism and the start and stop dates 
for their most recent TRT. In addition, start dates for the use of any medications for hypertension, 
taken > 3 months within screening will be recorded in the CRF/eCRF. 
Eligible subjects must have a screening mean sBP < 150 mm Hg and/or dBP < 90 mm Hg. 
Subjects taking prescribed antihypertensives should be taking medications on the day of the 
screening visit with sips of water; the medication should be noted as a prior medication. Subjects < 
60 years of age and prescribed antihypertensives will be excluded if the mean of the triplicate 
assessment of sBP > 140 mm Hg and/or dBP > 90 mm Hg at screening. Any increase in the dose 
of the antihypertensive medication or any need to add new antihypertensive medications should be 
considered an AE and recorded in the CRF/eCRF. 
8.4.7.1 Prohibited Medication/Therapy 
Subjects must remain off all forms of T except for study drug throughout the entire study. Use of 
dietary supplements such as saw palmetto or phytoestrogens as well as any dietary supplements 
that may affect total T levels such as androstenedione or dehydroepiandrosterone during the study 
is not permitted. Use of antiandrogens, 5-alpha-reductase inhibitors (eg, dutasteride, finasteride), 


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estrogens or long-acting opioid analgesics (eg, methadone hydrochloride, buprenorphine 
hydrochloride) are not permitted during the study. 
8.4.7.2 Other Restrictions 
During the Run-In Phase subjects will be advised to avoid taking oral study drug while fasting (ie, 
“on an empty stomach”). Subjects should take the oral TU immediately before the breakfast and 
dinner meals. While in the clinic or Phase 1 unit during the PK Phase, subjects will be required to 
consume the entire protocol-defined breakfast and dinner meals within 20 minutes after taking oral 
TU. 
Subjects will be asked to refrain from consuming grapefruit, grapefruit juice, or grapefruit 
supplements while on study drug. 
Subjects will be asked to observe all rules and smoking restrictions in place at the clinical facility 
during confinement. 
8.4.8 Treatment Compliance 
Subjects will return their unused study medication and compliance with study drug will be 
assessed on Day 14 of the Run-In Phase following the PM dose. Significant non-compliance with 
treatment during the Run-in Phase (<80% or > 120% compliant) will be documented as a protocol 
deviation. During the PK Phase dosing administration will be observed and compliance assessed.  
Any deviation from the prescribed dosage regimen will be recorded. In cases of significant non-
compliance, a subject may be discontinued from the study at the investigator’s and sponsor’s 
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9 
TIMING OF STUDY PROCEDURES 
Subjects will provide written informed consent before any study-related procedures are performed.  
9.1 
Screening Phase 
9.1.1 Screen 1 Day -28 to -7 
Screening of all subjects will be performed up to 28 days of the initial dose of study drug to assess 
subject eligibility. After the subject provides signed informed consent, the procedures of the 
Screen 1 visit will include: 
 Assess for eligibility (against the inclusion and exclusion criteria) 
 Record medical history, including concomitant illnesses/diseases. The subject’s medical 
history (key events) will be recorded on the Medical History CRF/eCRF. If a clinical event 
concerns a chronic disorder, which means it started in the past and it is still present at the 
screening visit, it should also be recorded on the Medical History CRF/eCRF. 
 Record concomitant medications. Medication use (prescription and/or over-the-counter, 
including vitamins and herbal supplements) from 3 months before study drug administration 
through the end of the study will be recorded on the Concomitant Medication eCRF. If a 
subject reports taking any over-the-counter or prescription medications, vitamins and/or 
herbal supplement or if administration becomes necessary from 3 months before study drug 
administration through the end of the study, the name of the medication, dosage information 
including dose, route, frequency, date(s) of administration including start and end dates, and 
reason for use must be recorded. For any medications taken after study drug administration 
and through the end of the study, the subject may continue to participate in the study only 
after the investigator agrees the subject may continue. 
 Subjects will be asked about their treatment history for hypogonadism and the start and stop 
dates of their most recent TRT. 
 Record demographic data, such as ethnic origin, and date of birth. 
 Obtain height, weight and BMI. 
 Record vital signs (sitting BP and heart rate [HR] in triplicate). If the subject is taking 
antihypertensives, then these medications should be taken on the morning of the visit with 
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 Ensure adequate venous access in the left or right arm to allow collection of a number of 
blood samples via a venous cannula. 
 
 Collect samples for hematology, clinical chemistry, and urine dipstick after subjects have 
fasted overnight. Eligibility laboratory tests will include complete blood count, chemistry 
panel, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, 
creatinine, lipids, and albumin. 
 
 Obtain PSA 
 
 A glycosylated hemoglobin test will be performed for diabetic subjects only.  
 
 Obtain blood sample for total T determination between 6:00 and 10:00 AM. 
9.1.2 Screen 2 approximately 7 (±2) days post Screen 1 
The Screen 2 visit should occur between 6:00 and 10:00 AM, approximately 7 (2±) days after the 
Screen 1 visit, and after results from the Screen 1 total T value have been received. Subjects should 
return for the Screen 2 visit only if the Screen 1 visit total T is < 300 ng/dL and no exclusionary 
values for safety are identified. No rescreening will be allowed for T levels ≥ 300 ng/dL.  
The Screen 2 assessments include: 
 Assess for eligibility (against the inclusion and exclusion criteria). 
 Record any changes in prior and concomitant medications. 
 Perform a physical examination (including DRE).  
 Obtain blood sample for the second total T determination approximately 7 days after the 
initial sample, between 6:00 and 10:00 AM.  
 Review for AEs.  
9.2 
Run-In and PK Phases 
9.2.1 Run-In Phase (14±2 Days) 
During the Run-In Phase, subjects will be instructed to take study drug BID just before the 
morning (breakfast) and evening (dinner) meals approximately 12 hours apart, which will suppress 
subjects’ endogenous testosterone production while allowing the oral TU to reach steady state.   


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9.2.2 Run-In Phase Dosing Day 1  
Once it has been confirmed the subject’s total T values at the Screen 1 and Screen 2 visits meet 
eligibility criteria (morning total T values of <300 ng/dL [obtained between 6:00 and 10:00 am] 
drawn on 2 separate days approximately 7 (±2) days apart), the subject will be asked to return to 
the clinic for Run-In Dosing Day 1 prior to breakfast (ie, overnight fast). No rescreening will be 
allowed for total T levels ≥ 300 ng/dL. Study center personnel will review prior and concomitant 
medications.  
The following Run-In Dosing Day 1 procedures should be performed pre-dose: 
 Assess for eligibility (against the inclusion and exclusion criteria) and if the subject meets 
eligibility 
 Collect safety laboratory tests after an overnight fast.  
 Collect pre-dose blood samples for T, DHT and TU concentrations.  
 Record vital signs [sitting BP and heart rate (HR) in triplicate]. Obtain vital signs prior to 
blood draws. 
 Perform a brief physical examination. 
 
 Dispense one bottle of 237 mg capsules and instruct subject to take first dose immediately 
prior to the breakfast, which will be provided at the clinic. Document in drug accountability 
record.   
 Instruct subjects to take study medication twice-daily immediately before breakfast and 
dinner meals each day. Subjects will be instructed to maintain their regular diet throughout 
the Run-In Phase. 
 Instruct subjects to bring all study drug with them to the clinic the evening of Run-In Dosing 
Day 14 (±2) prior to the evening dose and meal.   
 Assess for AEs and changes in concomitant medications. 
9.2.3 Run-In Phase, Dosing Day 14 (±2) 
Subjects should not take their PM dose or eat before arrival at the overnight clinic in the evening 
of Run-In Phase Dosing Day 14. Vital sign measurements will be obtained (sitting BP and HR in 
triplicate) prior to blood draws. Site personnel will confirm that each subject has taken his dose of 


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concomitant medications (with sips of water) and morning dose of study medication. Subjects will 
be administered their evening dose of study medication immediately prior to the provided, 
protocol-defined evening meal at the clinic.  Site personnel will document any changes in 
concomitant medications and assess any previous and/ or new AEs, collect study medication and 
complete drug accountability and determine adequate treatment compliance to proceed with the in-
patient PK Phase (>80% compliance). Subjects will take their study dose immediately prior to the 
protocol-defined meal provided at the Clinic.  Study drug accountability will be performed 
following the PM dose. 
9.2.4 PK Phase/Periods 1, 2, 3, 4, and 5  
Each participating site will receive a bottle containing 120 capsules of 237 mg TU from which to 
dispense study medication to subjects during Periods 1 through 5 of the PK Phase.   
Vital sign measurements will be obtained (sitting BP and HR in triplicate) and site personnel will 
confirm that each subject has taken his dose of concomitant medications (with sips of water).  
Blood samples for hematology and clinical chemistry will be collected prior to breakfast. Subjects 
will be administered their morning dose immediately prior to the protocol-defined breakfast, 
except for fasting period.  Study personnel will provide 1 of 4 defined breakfasts or a 240 mL glass 
of water (for the fasting treatment) on Periods 1 through 5.  Study personnel will provide 
standardized lunch and protocol-defined dinner meals. Subjects will be instructed to consume 
entire breakfast and dinner meals within 20 minutes.   Subjects will be administered their evening 
dose immediately prior to the protocol-defined dinner.  Subjects should not consume food within 
10 hours prior to the next morning dose during the PK Phase. 
Serial blood samples will be collected over 24 hours. Samples will be collected as follows:, 0 (pre-
morning dose), 2, 4, 6, 9, 12, 14, 16, 18, 21, and 24 hours after morning dose  (serial sampling 
times are relative to the AM dose). The 24-hour sample collection following dosing on Days 1, 2, 
3, and 4 will also serve as the 0 (pre-dose) samples on Days 2, 3, 4, and 5, respectively. Blood 
sample collection should be performed within ±10 minutes of the scheduled time points (with the 
exception of the 0-hour time point for each treatment during the PK Phase which should be 
collected within 5 minutes before oral TU dose administration.  Dose administration, meal times 
and sample collection times will be recorded.  
The subject will be asked to consume the entire breakfast (except during fasting Period) and dinner 
meals within 20 minutes. If unable to consume the entire meal, the subject will return any 
unconsumed portion of the meal to the site personnel who record the unconsumed portion. In 
addition to PK blood sampling, the subject will be assessed for AEs. Subjects will be instructed to 
take their concomitant medications every morning before breakfast (or fasting). Subjects should 


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maintain their current prescribed concomitant medication schedule.  Strenuous activity during 
confinement will not be permitted.    
9.2.5 PK Phase on Day 6 (Discharge from Unit) 
Subjects will be released from the clinic after the 24-hour blood draw following the 5th treatment 
period of the PK Phase (ie. PK Day 6). Vital signs will be measured (sBP, dBP, HR in triplicate) at 
least 30 minutes prior to collecting the final PK sample.  Complete fasting safety laboratory tests 
will be obtained at the time of the 24 hour PK sample.  A brief physical exam will be performed 
and AEs will be assessed.  Subjects will be provided with a non-protocol defined morning meal 
before being discharged from the unit.   
9.2.6 Safety Follow-up Phase (5 to 7 days post last-dose) 
Subjects should be contacted (or seen if necessary) 5 to 7 days after their final dose to assess the 
following: 
 Report of an AE that requires further evaluation. 
 Repeat of an abnormal laboratory value or for a laboratory result that requires additional 
follow up. 
 Repeat complete blood count for any subject with an elevated HCT value over 54% on PK 
Phase Period 5. Elevated HCT will be followed to resolution.  
 Subject may be contacted by telephone for this safety assessment if no follow up laboratory 
work or assessment of adverse events is required. 
9.3 
Early Withdrawal Visit 
Subjects who withdraw from treatment or the study will be asked to undergo the early withdrawal 
assessments and procedures including a physical examination, vital sign measurements (sitting BP 
and HR in triplicate), review for concomitant medications, AEs, and drug accountability, and if 
possible, blood samples for complete safety laboratory tests. Subjects should return all study drugs. 


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9.4 
PK Phase Meals 
Subjects will be admitted to the clinic the evening of Run-in Phase Dosing Day 14 (±2). Subjects 
will be provided all meals during the PK Phase and will be confined in the clinic. The protocol 
defined breakfast must follow the exact order of the randomly assign sequence (see Section 8.4.6). 
The subjects will take a single 237 mg TU capsule immediately before the protocol-defined 
breakfast and again immediately before the protocol-defined evening meal  (See Appendix D for 
all protocol-defined meals). Subjects will be asked to consume their entire protocol-defined 
breakfast and dinner meals within 20 minutes.  Subjects will be provided with standardized mid-
day during the PK Phase. Subjects will be offered a selection of protocol-defined lunch and dinner 
meals (included in Appendix D).  Subjects may select any meal from those available and described 
in the protocol-defined lunch and dinner list, but must be served and consume the assigned 
breakfast meal according to the randomly assigned sequence.  Meals will be scheduled at the same 
time on each day of the PK Phase. Doses of study drug will be administered immediately before 
breakfast and dinner. The subject will fast, except for water, until 4 hours post-AM dose when he 
can eat lunch.  Water is allowed as desired except for one hour before and after the protocol-
defined meals. 
9.5 
Duration of Subject Participation 
The duration of subject participation in the study will be up to approximately 56 days 
(approximately 8 weeks), including 
 Up to a 28-day Screening Phase; 
 A 14-day Run-In Phase; and 
 A 6-day PK Phase; and  
 A 5 to 7-Day Safety Follow up Phase. 


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10 PHARMACOKINETICS AND SAFETY VARIABLES 
10.1 
Pharmacokinetic Variables 
Serial blood sampling for total T, DHT and TU will be collected throughout PK Phase Periods 1 
through 5.  Samples will be collected at the following times:  0, 2, 4, 6, 9, 12, 14, 18, 21 and 24 
hours post the AM dose on each day that a treatment (meal type) is administered.  
The concentrations of total T, DHT and TU collected following each of the defined breakfast 
meals will be analyzed to derive the PK parameters of Cmax, time to maximum concentration 
(Tmax), area under the plasma concentration-time curve over the 12-hour dosing interval (AUC12) 
following the AM dose.  
The time of dose administration and the timing of each blood sample collection will be recorded to 
the minute (nominal scheduled time points are listed in Table 1). Blood sample collection should 
be performed within ± 10 minutes of the scheduled time points (with the exception of the 0-hour 
time point which should be within 5 minutes before oral TU dose administration on each PK Phase 
treatment day). 
Table 1 
Timing of Blood Samples 
Study Visit  
Analytes 
Blood Samples Assay Time Points* 
PK Phase Period 1/ Day 1 Total T, DHT and TU 0 (pre-morning dose), 2, 4, 6, 9, 12, 14, 16, 18, 21, and 24 
hours after morning dose 
PK Phase Period 2/ Day 2 Total T, DHT and TU 0 (pre-morning dose), 2, 4, 6, 9, 12, 14, 16, 18, 21, and 24 
hours after morning dose 
PK Phase Period 3/ Day 3 Total T, DHT and TU 0 (pre-morning dose), 2, 4, 6, 9, 12, 14, 16, 18, 21, and 24 
hours after morning dose 
PK Phase Period 4/ Day 4 Total T, DHT and TU 0 (pre-morning dose), 2, 4, 6, 9, 12, 14, 16, 18, 21, and 24 
hours after morning dose 
PK Phase Period 5/ Day 5 Total T, DHT and TU 0 (pre-morning dose), 2, 4, 6, 9, 12, 14, 16, 18, 21, and 24 
hours after morning dose 
*The 24 hours sample on Days 1-4 serve as the 0 hour samples for Days 2-5. 
Note: Blood samples for Total T, DHT and TU determination are collected in tubes containing sodium fluoride and EDTA (NaF-
EDTA). 
A certified laboratory will process samples and provide results for the hormone assays throughout 
the study. The certified study laboratory will provide information for sample collection and 
shipment and contact information in the Laboratory Manual. 
 


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10.2 
Safety Variables 
10.2.1 Adverse Events 
The investigator will monitor each subject for clinical and laboratory evidence of AEs on a routine 
basis throughout the study. The investigator will assess and record any AE in detail including the 
date of onset, event diagnosis (if known) or sign/symptom, severity, time course, duration, 
outcome, relationship of the AE to study drug, and any action(s) taken. For serious AEs not 
considered "related" to study drug, the investigator will provide an “Other” cause of the event. For 
AEs to be considered intermittent, the events must be of similar nature and severity. Adverse 
events, whether in response to a query, observed by site personnel, or reported spontaneously by 
the subject will be recorded. All AEs will be followed to a satisfactory resolution. 
10.2.1.1 Adverse Event Definition 
An AE is defined as any untoward medical occurrence in a clinical study subject administered a 
medicinal product that does not necessarily have a causal relationship with this treatment. An AE 
can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a medicinal (investigational) product, 
whether or not it is related to the medicinal (investigational) product. This includes an exacerbation 
of pre-existing conditions or events, intercurrent illnesses, drug interaction or the significant 
worsening of the indication under investigation that is not recorded elsewhere in the CRF/eCRF 
under specific efficacy assessments. Anticipated fluctuations of pre-existing conditions, including 
the disease under study, that do not represent a clinically significant exacerbation or worsening 
need not be considered AEs. 
The investigator is responsible for documenting all AEs that occur during the study. Adverse 
events will be elicited by asking the subject a non-leading question, for example, “Have you 
experienced any new or changed symptoms since we last asked/since your last visit?” Adverse 
events should be reported on the appropriate page of the CRF/eCRF. 
10.2.1.2 Assessment of Severity 
Each AE will be assigned a category by the investigator as follows: 
Mild: 
An AE that is easily tolerated by the subject, causes minimal discomfort, 
and does not interfere with everyday activities. 
Moderate: 
An AE that is sufficiently discomforting to interfere with normal 
everyday activities; intervention may be needed. 
Severe: 
An AE that prevents normal everyday activities; treatment or other 
intervention usually needed. 


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If there is a change in severity of an AE, it must be recorded as a separate event. 
10.2.1.3 Assessment of Causality 
Every effort will be made by the investigator to assess the relationship of the AE, if any, to the 
study drug. Causality should be assessed using the categories presented in the following table: 
Definitely not 
related: 
Clinical event with an incompatible time relationship to study drug 
administration, and that could be explained by underlying disease or 
other drugs or chemicals or is incontrovertibly not related to the study 
drug. 
Probably not 
related: 
Clinical event whose time relationship to study drug administration 
makes a causal connection improbable, but that could plausibly be 
explained by underlying disease or other drugs or chemicals. 
Possibly related: Clinical event with a reasonable time relationship to study drug 
administration, but that could also be explained by concurrent disease 
or other drugs or chemicals. 
Probably related: Clinical event with a reasonable time relationship to study drug 
administration, and is unlikely to be attributed to concurrent disease 
or other drugs or chemicals. 
Definitely: 
Clinical event with plausible time relationship to study drug 
administration, and that cannot be explained by concurrent disease or 
other drugs or chemicals 
10.2.1.4 Action Taken 
The investigator will describe the action taken in the appropriate section of the CRF/eCRF, as 
follows: 
 
Drug withdrawn 
 
Drug interrupted 
 
Other, specify 
10.2.1.5 Follow-up of Adverse Events 
All investigators should follow up subjects with AEs until the event is resolved or until, in the 
opinion of the investigator, the event is stabilized or determined to be chronic. Details of AE 
resolution must be documented in the CRF/eCRF. 


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Any open AEs at the end of the study should be followed up for 7 days after the subject receives 
the last dose of study drug, and any spontaneous AEs that occur during this time should be 
reported according to the procedures outlined above. 
Pregnancy 
Subjects will be instructed that known or suspected pregnancy occurring during the study, in 
female partners of study subjects, should be confirmed and reported to the investigator. The 
investigator should also be notified of pregnancy occurring during the study but confirmed after 
completion of the study. In the event that a female partner of a study subject is subsequently found 
to be pregnant, any pregnancy will be followed to term, and the status of mother and child will be 
reported to the sponsor after delivery. 
10.2.1.6 Documentation and Reporting of Adverse Events 
AEs should be reported and documented in accordance with the procedures outlined below. All 
AEs occurring during the study must be documented on the relevant CRF/eCRF pages. The 
following data should be documented for each AE: 
 
Description of the symptom event 
 
Classification as “serious” or “not serious” 
 
Severity 
 
Date of first occurrence and date of resolution (if applicable) 
 
If the date of first occurrence is on or after date of initial dosing, the AE is regarded as 
“treatment emergent”. 
 
Action taken 
 
Causal relationship 
 
Outcome of event (unknown, recovered, not yet recovered, recovered with sequelae, death 
[with date and cause reported]) 
10.2.2 Serious Adverse Events (SAE) 
10.2.2.1 Serious Adverse Event Definition 
An SAE is any untoward medical occurrence or effect that, at any dose, 


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 
Results in death. 
 
Is life threatening (an AE is life threatening if the subject was at immediate risk of death 
from the event as it occurred, ie, it does not include a reaction that might have caused death 
if it had occurred in a more serious form). 
 
Requires or prolongs inpatient hospitalization. (Complications occurring during 
hospitalization are AEs and are SAEs if they cause prolongation of the current 
hospitalization. Hospitalization for elective treatment of a pre-existing non-worsening 
condition is not, however, considered an AE. The details of such hospitalizations must be 
recorded on the medical history or physical examination page of the eCRF). 
 
Results in persistent or significant disability/incapacity. (An AE is incapacitating or disabling 
if it results in a substantial and/or permanent disruption of the subject’s ability to carry out 
normal life functions). 
 
Results in a congenital anomaly/birth defect of an offspring or a female partner or a study 
subject. 
In addition, medical and scientific judgment is required to decide if prompt notification is required 
in situations other than those defined for SAEs above. This may include any event that the 
investigator regards as serious that did not strictly meet the criteria above but may have 
jeopardized the subject or required intervention to prevent one of the outcomes listed above, or that 
would suggest any significant hazard, contraindication, side effect, or precaution that may be 
associated with the use of the investigational product. 
10.2.2.2 Reporting of Serious Adverse Events 
Any SAE must be reported by the investigator if it occurs during the clinical study or within 7 days 
of receiving the study drug, whether or not the SAE is considered to be related to the 
investigational product. An SAE report consists of the SAE form, the AE form, and the 
concomitant medication form. A copy of these forms must be faxed within 24 hours for the 
attention of the product safety scientist at: 
The investigator should not wait to receive additional information to document fully the event 
before notification of a SAE, though additional information may be requested. Where applicable, 
information from relevant laboratory results, hospital case records, and autopsy reports should be 
obtained. 


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Instances of death, congenital abnormality, or an event that is of such clinical concern as to 
influence the overall assessment of safety, if brought to the attention of the investigator at any time 
after cessation of study drug administration and linked by the investigator to this study, should be 
reported to the study monitor. 
The sponsor will promptly notify all relevant investigators and the regulatory authorities of 
findings that could adversely affect the safety of subjects, impact on the conduct of the study or 
alter the institutional review board (IRB) approval/favorable opinion of the study. The sponsor, 
will expedite the reporting to all concerned investigators, to the IRBs, where required, and to the 
regulatory authorities of all adverse reactions that are both serious and unexpected. 
10.2.3 Clinical Laboratory  
The hematology and clinical chemistry laboratory analyses will be performed by certified 
laboratories. Reference ranges will be supplied by each laboratory and used by the investigator to 
assess the laboratory data for clinical significance and pathological changes. 
10.2.3.1 Hematology, Chemistry, and Urine Dipstick 
Blood samples for the clinical safety laboratory tests will be collected at Screening 1 and on PK 
Phase Period 5 (refer to Schedule of Assessments Table in Appendix A). Samples for serum 
chemistry tests will be collected in the morning after obtaining vital signs and after overnight 
fasting, but before meals and study drug administration. The test results from screening will serve 
as the baseline for future clinical assessments. 
Certified laboratories will process and provide results for the tests conducted at screening and 
throughout the study. The certified study laboratories for sample shipment and contact information 
are provided in the Laboratory Manual. 


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Table 2 
Listing of Clinical Laboratory Tests 
Hematology 
Clinical Chemistry 
Urine Dipstick 
Hematocrit 
Hemoglobin 
Red blood cell (RBC) count 
White blood cell (WBC) count  
Neutrophils bands (if detected)  
Lymphocytes  
Monocytes  
Basophils (if detected)  
Eosinophils (if detected)  
Absolute platelet count  
Mean corpuscular hemoglobin 
(MCH)  
Mean corpuscular volume (MCV)  
Mean corpuscular hemoglobin 
concentration (MCHC)  
Serum glutamic-pyruvic transaminase 
(SGPT/ALT) 
Serum glutamic-oxaloacetic 
transaminase (SGOT/AST) (screening) 
Alkaline phosphatase 
Sodium  
Potassium 
Bicarbonate 
Glucose 
Calcium  
Total Cholesterol  
Triglycerides  
Chloride  
High-density lipoprotein (HDL) 
cholesterol  
Low-density lipoprotein (LDL) 
cholesterol  
Bilirubin (screening) 
Glycosylated hemoglobin (screening) 
Creatinine 
Albumin 
Leukocytes 
Nitrite 
Specific gravity  
Ketones  
pH  
Protein  
Blood (hemoglobin) 
Glucose  
Urobilinogen  
Bilirubin 
 
Any laboratory test value obtained during the treatment phases that falls outside the reference 
range that the investigator considers to be clinically significant will be repeated to verify the 
out-of-range value and will be followed to a satisfactory clinical resolution. Investigators may 
consider laboratory abnormalities which are considered clinically significant to be AEs. A 
laboratory test value that requires a subject to be discontinued from the study or requires a subject 
to receive treatment will be recorded as an AE. Clinical laboratory testing must be performed by 
appropriately credentialed laboratory. 
10.2.3.2 Prostate-Specific Antigen 
Blood samples for PSA will be collected at Screening 1 and PK Phase Period 5 prior to discharge 
from the clinical facility. The blood sample must be collected before a DRE (if a DRE is also 
performed). 
10.2.4 Vital Sign Measurements 
Body temperature, BP and HR will be measured at screening and daily during the PK Phase. (see 
Appendix A). The vital sign measurements at screening will serve as the baseline measurements 
for clinical assessments. The subject should be sitting at rest for at least 5 minutes with his feet 
resting on the floor and before the BP and HR being measured 3 times at 1 to 2 minute intervals. 


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Blood pressure should be obtained prior to blood draws and measured by an automated, 
oscillometric device in the non-dominant arm, using a cuff that is appropriate for the size of the 
arm (during the course of the study, the same size cuff for the subject should be used). Study 
center personnel should ensure that there has been no recent caffeine or cigarette exposure (within 
30 minutes of reading) and that the subject’s bladder is empty. During BP measurements, the arm 
should be supported so that the bottom of the cuff is at the height of the heart (1 to 2 cm above the 
elbow). The cuff bladder (the part that inflates) should encircle at least 80% of the arm, if in doubt 
a larger cuff should be used. Whenever possible, the cuff should be in contact with skin, or very 
light clothing. Neither the subject nor the person measuring the BP should talk during the BP 
assessment. Study center personnel should explain the need to remain silent for accurate readings 
in advance.   
10.2.5 Physical Examination 
A complete physical examination will be performed at Screen 2. A brief examination will be 
performed at the conclusion of PK Phase Period 5 and will include at minimum examination of 
head/eyes/ears/nose/throat. Height and weight will be measured at screening only. The subject will 
wear lightweight clothing and no shoes. Subject's height and weight will be used to calculate BMI. 
For all subjects, a symptom-directed physical examination will be performed when necessary. Any 
relevant findings from the physical examination during screening will be recorded on the Medical 
History CRF/eCRF (for findings from the past). Any significant physical examination findings 
after dosing will be recorded as AEs. 
10.2.6 International Prostate Symptom Score (I-PSS) 
The I-PSS, a validated questionnaire used to assess the severity and impact of urinary symptoms, 
will be used to exclude subjects with moderate to severe symptoms of benign prostate hypertrophy 
(Appendix C). Subjects will complete the I-PSS provided by the sponsor as defined in the 
Schedule of Assessments Table (Appendix A). The screening I-PSS score (total I-PSS) must be ≤ 
19 to meet eligibility requirements. The I-PSS questionnaire will be repeated for early withdrawal 
subjects. 
10.3 
Handling and Processing of PK Blood Sample Collections 
Results from a recent study evaluating the degradation of TU to T in conditions typically used in 
clinical studies showed that for subjects receiving oral TU, the analysis of T in blood collected in 
red top tubes to separate serum causes overestimation of T exposure. This overestimation occurs 
because of the ex vivo conversion of TU to T by non-specific esterases in blood. Ex vivo 
conversion can be minimized by collecting blood into tubes that contain the esterase inhibitor 


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sodium fluoride (NaF), by immediately placing the samples on ice after collection, and by 
processing the samples at 4°C. Therefore analysis of T and TU in plasma, combined with the 
addition of NaF in the sample collection tube as an esterase inhibitor is being used in this study.10 
The total volume of blood to be collected from each subject during the study will not exceed 
approximately 500 mL. Details on the handling and processing of samples are provided in the 
Laboratory Manual. 
10.4 
Appropriateness of Measurements 
The PK and safety assessments planned for this study are widely used and generally recognized as 
reliable, accurate, and relevant for a pharmacokinetics and tolerability study. 


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11 STATISTICAL METHODS 
11.1 
Statistical and Analytical Plans 
The PK, and safety variables and associated analyses are described in this section.  
General methodology will include descriptive tabular and/or graphical summarizations by meal 
type at each dosing session of the PK Phase. Continuous variables will be presented using the 
descriptive statistics of number of observations (n), mean, standard deviation, standard error of the 
mean, median, minimum, and maximum values. Categorical values will be summarized with 
counts and percentages.  
All collected data will be presented in listings. 
11.2 
Pharmacokinetic Endpoints 
The pharmacokinetics of total T will be assessed by using noncompartmental analysis to analyze 
the total T concentrations from PK samples collected during each of the 5 treatment periods within 
the PK Phase of the study. The primary comparison of interest will be the dosing interval 
following the five protocol defined breakfasts (AM dose).  The total T PK parameters to be 
assessed within each relevant dosing interval will be peak concentration (Cmax), the time of peak 
concentration (Tmax), the area under the curve over the dosing interval (AUC12) and the time-
weighted average total T concentration (Cavg).  Also to be calculated, when sufficient concentration 
data exist, will be the analogous parameters for the dosage interval following the PM dose of TU 
during each of the 5 treatment periods within the PK Phase, and the analogous PK parameters 
(Cmax, Tmax, AUC24 and Cavg) for the combined 24-hour period that includes both the AM and the 
PM doses of TU for each specific treatment period. 
The concentrations and pharmacokinetic parameters for the individual subjects will be listed, and 
tabular summaries provided by treatment, along with appropriate descriptive statistics.  
The 30 gram fat breakfast treatment will serve as the reference meal in the comparisons to identify 
the effect of meal type on Cmax, AUC12 and Cavg for total T.  Subjects must have consumed the 
reference meal containing 30 g fat and at least one other treatment meal during the PK Phase, and 
to be evaluable for at least Cmax or AUC12 with respect to those minimum two meals in order to be 
included in the PK population.  
An analysis of variance (ANOVA) will be performed on the natural logarithms of Cmax, AUC12 and 
Cavg with treatment received, sequence, and period as fixed effects and subject as a random effect 
within sequence.  Treatment carryover effects will be estimated by testing sequence using subjects 
within sequence as the error term. Two-way contrasts will be made using the 30 g fat meal as the 


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reference treatment, and the point estimate and 90% confidence interval (CI) for the least squares 
(LS) mean difference in PK parameters on the log scale between the contrasted treatments will be 
exponentiated to obtain estimates for ratios of LS geometric means on the original scale. No food 
effect will be concluded for a contrasted treatment if the 90% CI about the ratio of LS geometric 
means of Cmax and AUC12 for that contrast lie totally within the 0.80 to 1.25 interval. 
11.3 
Safety Endpoints 
11.3.1 Systolic Blood Pressure  
Observed values in vital sign measurements, including sBP, dBP, HR, and changes from baseline 
in sBP, dBP, and HR will be summarized at each scheduled collection visit. 
11.3.2 Other Safety Endpoints 
Other key safety endpoints are:  
 Incidence of AEs 
 Change in physical examination findings 
 Change in vital sign measurements 
 Change in clinical laboratory tests, including hematocrit, and PSA. 
All safety endpoints will be analyzed using the safety population except if otherwise defined..  
Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
version 15.1. An AE is considered treatment-emergent if it begins or worsens in severity after the 
first dose of randomized study drug. The number and percentage of subjects with treatment 
emergent adverse events (TEAEs) will be tabulated by system organ class (SOC) and preferred 
term. A summary of the number of subjects with TEAEs will be provided by severity and by 
relationship to study drug. If for any AE severity and/or relationship to drug is missing, then the 
least favorable choice(s) (Severe and Definitely) will be assigned for purposes of tabulation and 
listing.  Subjects reporting more than 1 AE for a given MedDRA preferred term will be counted 
only once for that term using the most severe incident. Subjects reporting more than 1 type of 
event within an SOC will be counted only once for that SOC. Incidence of TEAEs, serious TEAEs, 
TEAEs resulting in discontinuation from study drug, and TEAEs resulting in death will be 
summarized. Listings will be provided for all AEs, SAEs, and AEs resulting in treatment 
discontinuation. 
Physical examination and results will be summarized at each scheduled visit.  


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Laboratory tests will be performed at screening 1 and at Day 6 and will be summarized are noted 
in Section 10.2.3. 
11.4 
Other Variables 
11.4.1 Demographic and Other Baseline Characteristics 
Descriptive statistical methods will be used to tabulate and summarize demographics and baseline 
characteristics (age [years], race, ethnicity, height, weight, body mass index, I-PSS, etc.). 
11.4.2 Study Drug Exposure and Compliance 
Duration of treatment in days will be summarized for all subjects. The number of subjects who 
required termination of study drug treatment will be summarized. 
Compliance will be calculated as the actual number divided by the expected number of dosages.  
11.4.3 Medical and Medication History 
Medications and a complete medical history will be obtained at screening. These will serve as the 
baseline for future clinical assessments. 
11.4.4 Prior and Concomitant Medications 
Prior and concomitant medications will be coded using the September 2012 World Health 
Organization (WHO) Drug Dictionary. Prior medications will be defined as medications 
documented on the Prior and Concomitant Medications CRF/eCRF as having started and stopped 
before the first dose of any study drug. Concomitant medications will be defined as medications 
documented on the Prior and Concomitant Medications CRF/eCRF as having started after the start 
of study drug or having started before the start of study drug and continued on or after the first 
dose of any study drug. Prior and concomitant medications will be summarized in separate tables.  
All concomitant medications administered will be tabulated in a data listing. 
11.5 
Handling of Missing Data 
Missing PK concentrations will not be imputed. A missing concentration value adjacent to the 
existing Cmax will make a subject non-evaluable for Cmax and AUC calculations. If more than one 
concentration in sequence is missing the subject will be considered non-evaluable for AUCs, 
unless the missing concentrations are embedded in a series of assay results that are below the limit 
of quantitation (BLQ). Single embedded missing concentrations will be treated as missing and the 
affected AUCs calculated by extending the trapezoid to the next existing concentration. Leading, 


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trailing and embedded BLQ values will be treated as 0.5 x lower limit of quantitation (LLOQ) for 
T. Missing actual sample collection times may be replaced with nominal scheduled sample 
collection times based on case-by-case review.  
11.6 
Sample Size 
Approximately 20 hypogonadal subjects will be enrolled at two to three study centers. This 
number is based on the following considerations and assumptions: 
If 20 subjects are enrolled, approximately 16 subjects are expected to complete the PK Phase. 
11.7 
Protocol Deviations 
The investigator should not implement any deviation from the protocol without prior review and 
agreement by the sponsor and in accordance with the IRB and local regulations, except when 
necessary to eliminate an immediate hazard to study subjects. When a deviation from the protocol 
is deemed necessary for an individual subject, the investigator must alert one of the following 
people: 
Primary Contact 
Alternate Contact 
Theodore Danoff, MD, PhD  
Clarus Therapeutics, Inc. 
555 Skokie Blvd., Suite 340 
Northbrook, IL 60062 
United States 
(mobile) +1 215 219-7446 
(office) +1 847 562-4300 
Cheryl Demos Fludas 
Clarus Therapeutics, Inc. 
555 Skokie Blvd., Suite 340 
Northbrook, IL 60062 
United States 
(office) + 847 562-4300 
 
Such contact must be made as soon as possible to permit a review by the investigator/sponsor to 
determine the impact of the deviation on the subject and/or the study. Any significant protocol 
deviations affecting subject eligibility and/or safety must be reviewed and/or approved by the IRB, 
as applicable, before implementation. 
Deviations will be listed in the clinical study report.  


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12 QUALITY ASSURANCE AND QUALITY CONTROL 
12.1 
Audit and Inspection 
Study centers and study documentation may be subject to Quality Assurance audit during the 
course of the study by the sponsor or its nominated representative. In addition, inspections may be 
conducted by regulatory authorities at their discretion. 
12.2 
Monitoring 
Data for each subject will be recorded on a CRF/eCRF. Data collection must be completed for 
each subject who signs an informed consent form (ICF) and is administered study drug. 
In accordance with current Good Clinical Practice and International Conference on Harmonisation 
of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines, 
the study monitor will carry out source document verification at regular intervals to ensure that the 
data collected in the CRF/eCRF are accurate and reliable. 
The investigator must permit the monitor, the IRB, the sponsor’s internal auditors, and 
representatives from regulatory authorities direct access to all study-related documents and 
pertinent hospital or medical records for confirmation of data contained within the DRF/eCRFs. 
12.3 
Data Management and Coding 
Data Management and coding activities include setting up a relevant database and data transfer 
mechanisms, along with appropriate validation of data and resolution of queries.  
Study centers will enter data directly onto a paper CRF/eCRF for entry into a secure data base. All 
data must be verifiable against source documents at the study center. Data recorded directly on the 
CRF/eCRF will be identified and the CRF/eCRF will be considered the source document.  
Medical coding will use MedDRA version 15.1 for concomitant diseases and AEs and WHODrug 
dictionary dated September 2012 for concomitant diseases and AEs and WHODrug for 
medications. 
Missing or inconsistent data will be queried in writing to the investigator for clarification. 
Subsequent modifications to the database will be documented. 


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13 RECORDS AND SUPPLIES 
13.1 
Drug Accountability 
On receipt of the study drug, the investigator (or deputy) will conduct an inventory of the supplies 
and verify that study drug supplies are received intact and in the correct amounts. The investigator 
will retain a copy of this receipt at the study center and return the original receipt to the study 
monitor. The monitor may check the study supplies at each study center at any time during the 
study. 
It is the responsibility of the study monitor to ensure that the investigator (or deputy) has correctly 
documented the amount of the study drug received, dispensed, and returned on the dispensing log 
that will be provided and that the drug is stored properly. A full drug accountability log will be 
maintained at the study center at all times. The study monitor will perform an inventory of study 
drug at the close-out visit to the study center. All discrepancies must be accounted for and 
documented. 


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14 ETHICS 
14.1 
Institutional Review Board 
Before initiation of the study at each study center, the protocol, the ICF, other written material 
given to the subjects, and any other relevant study documentation will be submitted to the 
appropriate IRB. Written approval of the study and all relevant study information must be obtained 
before the study center can be initiated or the study drug is released to the investigator. Any 
necessary extensions or renewals of IRB approval must be obtained for changes to the study such 
as amendments to the protocol, the ICF or other study documentation. The written approval of the 
IRB together with the approved ICF must be filed in the study files. 
The investigator will report promptly to the IRB any new information that may adversely affect the 
safety of the subjects or the conduct of the study. The investigator will submit written summaries 
of the study status to the IRB as required. On completion of the study, the IRB will be notified that 
the study has ended. 
14.2 
Regulatory Authorities 
Relevant study documentation will be submitted to the regulatory authorities, according to 
local/national requirements, for review and approval before the beginning of the study. On 
completion of the study, the regulatory authorities will be notified that the study has ended. 
14.3 
Ethical Conduct of the Study 
The investigators and all parties involved in this study should conduct the study in adherence to the 
ethical principles based on the Declaration of Helsinki, Good Clinical Practice (GCP), ICH 
guidelines, and the applicable national and local laws and regulatory requirements. 
14.4 
Informed Consent 
The process of obtaining informed consent must be in accordance with applicable regulatory 
requirement(s) and must adhere to GCP. 
The investigator is responsible for ensuring that no subject undergoes any study-related 
examination or activity before that subject has given written informed consent to participate in the 
study. 
The investigator or designated personnel will inform the subject of the objectives, methods, 
anticipated benefits and potential risks and inconveniences of the study. The subject should be 
given every opportunity to ask for clarification of any points he does not understand and, if 
necessary, ask for more information. At the end of the interview, the subject will be given ample 


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time to consider the study. Subjects will be required to sign and date the ICF. After signatures are 
obtained, the ICF will be kept and archived by the investigator in the investigator’s study file. A 
signed and dated copy of the subject ICF will be provided to the subject or their authorized 
representative. 
It should be emphasized that the subject may refuse to enter the study or to withdraw from the 
study at any time, without consequences for their further care or penalty or loss of benefits to 
which the subject is otherwise entitled. Subjects who refuse to give or who withdraw written 
informed consent should not be included or continue in the study. 
If new information becomes available that may be relevant to the subject’s willingness to continue 
participation in the study, a new ICF will be approved by the IRB(s) (and regulatory authorities, if 
required). The study subjects will be informed about this new information and re consent will be 
obtained. 
14.5 
Subject Confidentiality 
Monitors, auditors, and other authorized agents of the sponsor and/or its designee, the IRB(s) 
approving this research, and the US FDA, as well as that of any other applicable agency(ies), will 
be granted direct access to the study subjects’ original medical records for verification of clinical 
study procedures and/or data, without violating the confidentiality of the subjects to the extent 
permitted by the law and regulations. In any presentations of the results of this study or in 
publications, the subjects’ identity will remain confidential. 
All personal data collected and processed for the purposes of this study should be managed by the 
investigator and his/her staff with adequate precautions to ensure confidentiality of those data, and 
in accordance with the Health Insurance Portability and Accountability Act10, applicable to 
national and/or local laws and regulations on personal data protection. 


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15 REPORTING AND PUBLICATION, INCLUDING ARCHIVING 
Essential documents are those that individually and collectively permit evaluation of the study and 
quality of the data produced. After completion of the study (end of study defined as the date of the 
last visit of the last subject), all documents and data relating to the study will be kept in an orderly 
manner by the investigator in a secure study file. This file will be available for inspection by the 
sponsor or its representatives. Essential documents should be retained for 2 years after the final 
marketing approval in an International Conference on Harmonization (ICH) region or for at least 
2 years since the discontinuation of clinical development of the investigational product. The 
sponsor is responsible for informing the study center when these documents no longer need to be 
retained. The investigator must contact the sponsor before destroying any study related 
documentation. In addition, all subject medical records and other source documentation will be 
kept for the maximum time permitted by the hospital, institution, or medical practice. 
The sponsor intends to work with investigators to collectively publish results of the study in a 
peer-reviewed medical journal where authorship generally will follow level of participation in the 
study. Furthermore, the sponsor must review and approve any results of the study or abstracts for 
professional meetings prepared by the investigator(s). Published data must not compromise the 
objectives of the study. Data from individual study centers in multicenter studies will not be 
published separately. 


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16 REFERENCES 
 
Guidance for Industry Food-Effect Bioavailability and Fed Bioequivalence Studies. (2002, December). 
Retrieved from http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126833.pdf. 
 
 
Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in adult men with androgen 
deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 
2010;95(6):2536–59. 
 
Griffin JE, Wilson JD. Disorders of the Testes. In: Isselbacher KJ, et al, editors. Harrison’s Principles 
of Internal Medicine. 13th ed. New York, NY: McGraw-Hill; 1994:2006-17.  
 
Braunstein GD. Testes. In: Greenspan FS, Gardner DG, et al, editors. Basic and C linical 
Endocrinology. New York, NY: McGraw-Hill; 2001:422-52. 
 
Bagatell CJ, Bremner WJ. Androgens in men – uses and abuses. N Eng J Med. 1996;334(11):707-
14.178. 
 
Malkin CJ, Pugh PJ, Jones RD, Jones TH, Channer. Testosterone as a protective factor against 
atherosclerosis – immunomodulation and influence upon plaque development and stability. J 
Endocrinol. 2003;178(3):373-80. 
 
Behre HM, Nieschlag E. Comparative pharmacokinetics of testosterone esters. In: Nieschlag E, Behre 
HM editors. Testosterone Action, Deficiency, Substitution. New York, NY: Springer-Verlag; 1998:329-
348. 
 
Lachance S, Dhingra O, Bernstein J, et al. Importance of measuring testosterone in enzyme-inhibited 
plasma for oral testosterone undecanoate androgen replacement therapy clinical trials. Future Sci OA. 
2015; 1(4):FSO55(doi: 10.4155/FSO.15.55). 
 
Clarus Therapeutics, Inc. Oral Testosterone Undecanoate. Investigator’s Brochure Edition 7.0. 
Northbrook, IL: Clarus Therapeutics, Inc.; 16 November 2015. 
 
US Department of Health and Human Services. The Health Insurance Portability and Accountability 
Act (HIPAA) of 1996 (P.L.104-191) [HIPAA]. http://aspe.hhs.gov/admnsimp/pl104191.htm. 
Effective August 21, 1996. 


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Appendices 
Appendix A. 
SCHEDULE OF ASSESSMENTS 
 


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Table 3 
Schedule of Assessments 
Activity 
Screening Phase 
Treatment Phase 
 
Safety Follow-Up 
Phase 
Screen 1 
Screen 2 
14 (±2) Day Run-In 
Phase 
PK Phase 
Phone or Clinic 
Visit a 
Day -28 
to -21 
Approx 7 
(±2) days 
post 
Screen 1 
Dosing 
Day 1
 
Dosing 
Day 14 
Period 1/
Day 1 
Period 2/ 
Day 2 
Period 3/
Day 3 
Period 4/
Day 4 
Period 5e/ 
Day 5-6 
5 to 7 Days post 
Last Dose 
Dosing 
Day 15
Dosing 
Day 16 
Dosing 
Day 17
Dosing 
Day 18 
Dosing 
Day 19 
Informed consent  
X 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Review 
X 
X 
X 
 
 
 
 
 
 
 
Medical History Review 
X 
 
 
 
 
 
 
 
 
 
Prior & Concomitant Meds  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical Examination with DRE 
 
X 
 
 
 
 
 
 
 
Xb 
Brief Physical Examination 
 
 
X 
 
 
 
 
 
Xf 
 
Weight, Height, and BMI 
X 
 
 
 
 
 
 
 
 
 
Adverse Event Assessment 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs (triplicate sitting BP 
& HR) 
X 
 
X 
 
X 
X 
X 
X 
X 
Xb 
Complete Safety Lab (fasting) 
(Period 5 labs will be drawn at 
the 24-hour post AM dose) 
X 
 
 
 
X 
 
 
 
X 
 
Xb 
Urine Dipstick 
X 
 
 
 
 
 
 
 
 
 
Serum Total Testosterone (T) 
between 6:00 and 10:00 AM   
(7±2 days apart) 
X 
X 
 
 
 
 
 
 
 
 


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Activity 
Screening Phase 
Treatment Phase 
 
Safety Follow-Up 
Phase 
Screen 1 
Screen 2 
14 (±2) Day Run-In 
Phase 
PK Phase 
Phone or Clinic 
Visit a 
Day -28 
to -21 
Approx 7 
(±2) days 
post 
Screen 1 
Dosing 
Day 1
 
Dosing 
Day 14 
Period 1/
Day 1 
Period 2/ 
Day 2 
Period 3/
Day 3 
Period 4/
Day 4 
Period 5e/ 
Day 5-6 
5 to 7 Days post 
Last Dose 
Dosing 
Day 15
Dosing 
Day 16 
Dosing 
Day 17
Dosing 
Day 18 
Dosing 
Day 19 
PSA (Period 5 PSA will be 
drawn at the 24-hour post AM 
dose) 
X 
 
 
 
 
 
 
 
X 
 
Study Meal Administration  
 
 
Xc 
Xc 
X 
X 
X 
X 
X 
 
Pre-dose Total T and DHT 
between 6:00 and 10:00 AM  
 
 
X 
 
 
 
 
 
 
 
Serial PK Sampling Total T, 
DHT and TU 
 
 
 
 
Xd 
Xd 
Xd 
Xd 
Xd 
 
I-PSS 
X 
 
 
 
 
 
 
 
 
 
Dispense Bottle of Study Drug  
 
 
X 
 
 
 
 
 
 
 
Dosing instructions given for 
BID dosing for Run-In Phase --
Day 1 PM Dose to Day 14 AM. 
Doses will be self-administered 
at home immediately prior to 
breakfast and dinner meals 
 
 
X 
 
 
 
 
 
 
 
In clinic Study Drug 
Administered AM 
 
 
Xc 
 
X 
X 
X 
X 
X 
 
In clinic Study Drug 
Administered PM 
 
 
 
Xc 
X 
X 
X 
X 
X 
 
Study Drug Accountability  
 
 
 
X 
X 
X 
X 
X 
X 
 


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a A visit done by telephone is acceptable if follow-up for safety issues (i.e. abnormal lab result, or adverse event) is not needed. 
b Collect sample or complete procedure if abnormal at Period 5 or needed as follow-up for a safety concern.  
c Subjects will take their AM dose on Day 1 and PM dose on Day 14 in the clinic with meals provided.  The doses will be dispensed from the bottle that was dispensed on Dosing Day 1.  Subjects 
will take their study dose immediately prior to the protocol-defined meal provided at the Clinic.  Study drug accountability will be performed following the PM dose on Day 14. 
d Blood samples for total T: Subjects will have 4 NaF-EDTA-containing tubes (for plasma) collected. Samples will be collected as follows:  0 (pre-morning dose), 2, 4, 6, 9, 12, 14, 16, 18, 21, and 
24 hours after morning dose. The 24-hour PK sample for Day 1, 2, 3, and 4 will also serve as the 0 (pre-dose) PK sample for Day 2, 3, 4, and 5, respectively. Samples following pre-morning dose 
must be drawn within 10 minutes of the nominal time relative to the AM dose taken each Period. 
e A brief physical examination will be performed and subjects will depart clinic the following morning on Day 6. No study medication will be administered after PK Phase Period 5. 


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Appendix B. 
INVESTIGATOR SIGNATURE PAGE 
Investigator Signature Page 
Protocol Title: 
A Phase 2 Study of the Effect of Meals with Various Amounts of Fat 
Given Immediately After Dosing on the Pharmacokinetics of an Oral 
Testosterone Undecanoate in Hypogonadal 
Protocol Number: 
CLAR-16015 
Confidentiality and cGCP Compliance Statement 
I, the undersigned, have reviewed this protocol (and amendments), including appendices, and 
I will conduct the study as described in compliance with this protocol (and amendments), 
GCP, and relevant ICH guidelines. 
Once the protocol has been approved by the IRB, I will not modify this protocol without 
obtaining prior approval of Clarus Therapeutics, Inc. and of the IRB. I will submit the 
protocol amendments and/or any ICF modifications to Clarus Therapeutics, Inc. and IRB, and 
approval will be obtained before any amendments are implemented. 
I understand that all information obtained during the conduct of the study with regard to the 
subjects’ state of health will be regarded as confidential. No subjects’ names will be 
disclosed. All subjects will be identified by assigned numbers on all CRF/eCRFs, laboratory 
samples, or source documents forwarded to the sponsor. Clinical information may be 
reviewed by the sponsor or its agents or regulatory agencies. Agreement must be obtained 
from the subject before disclosure of subject information to a third party. 
Information developed in this clinical study may be disclosed by Clarus Therapeutics, Inc., to 
other clinical investigators, regulatory agencies, or other health authority or government 
agencies as required. 
 
 
 
Investigator Signature 
 
Date 
 
 
 
Printed Name 
 
 
 
 
 
Institution 
 
 


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Appendix C. 
INTERNATIONAL PROSTATE SYMPTOM SCORE 
(I-PSS) 
International Prostate Symptom Score 
(I-PSS) 
INTERNATIONAL PROSTATE SYMPTOM SCORE (I-PSS) 
 
 
Not at all
Less Than 1 
Time in 5
Less Than 
Half the 
Time
About Half 
the Time
More Than 
Half the 
Time 
Almost 
Always
1 
Over the past month, how often have 
you had a sensation of not emptying 
your bladder completely after you 
finished urinating? 
0 
1 
2 
3 
4 
5 
2 
Over the past month, how often have 
you had to urinate again less than two 
hours after you finished urinating? 
0 
1 
2 
3 
4 
5 
3 
Over the past month, how often have 
you found you stopped and started 
again several times when you 
urinated? 
0 
1 
2 
3 
4 
5 
4 
Over the past month, how often have 
you found it difficult to postpone 
urination? 
0 
1 
2 
3 
4 
5 
5 Over the past month, how often have 
you had a weak urinary stream? 
0 
1 
2 
3 
4 
5 
6 
Over the past month, how often have 
you had to push or strain to begin 
urination? 
0 
1 
2 
3 
4 
5 
 
 
None
1 time
2 times
3 times
4 times 
5 or more 
times
7 
Over the past month, how many 
times did you most typically get up to 
urinate from the time you went to bed 
at night until the time you got up in 
the morning? 
0 
1 
2 
3 
4 
5 
Total I-PSS Score S = 


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(I-PSS continued) 
QUALITY OF LIFE DUE TO URINARY SYMPTOMS 
 
 
Delighted 
Pleased 
Mostly 
Satisfied 
Mixed About 
Equally 
Satisfied and 
Dissatisfied 
Mostly 
Dissatisfied Unhappy 
Terrible 
1 
If you were to spend the 
rest of your life with your 
urinary condition just the 
way it is now, how would 
you feel about that? 
0 
1 
2 
3 
4 
5 
6 
Quality of life assessment index L = 
International Prostate Symptom Score© (I-PSS©) Michael J. Barry, 1992. All rights reserved. 
 
 


Clarus Therapeutics, Inc.  
15 September 2016 
CLAR-16015 Version 1.0 
Page 62 of 68 
CONFIDENTIAL 
Appendix D. 
PROTOCOL DEFINED MEALS 
 
Meal
Food Description
Amount
Measure
Energy
Protein
Fat
Carbohydrate 
  KELLOGG'S FROSTED 
FLAKES
60 gram
221.4
2.38
1.01
53.52
Milk, lowfat, fluid, 1% 
milkfat, with added vitamin 
A and vitamin D
0.75 1 cup
76.86
6.17
1.78
9.13
Nature Valley Protein 
Chewy Bar
1
counted 
prepackage
190
10
12
14
Apple juice,  canned or 
bottled, unsweetened
8 1 fl oz
114.08
0.25
0.32
28.02
Chobani non fat fruit yogurt 
(150 gr)
1
counted 
prepackage
120
12
0
19
Motts Cinnamon 
Applesauce sweetened
1
counted 
prepackage
100
0
0
25
Actual
822.34
30.79
15.11
148.68
Goal
850.0
31.9
15.0
146.9
Thomas 100% Whole Wheat 
Bagel (95gr)
95 gram
240
11
1.5
45
Butter, salted
10 gram
71.7
0.09
8.11
0.01
Motts Cinnamon 
Applesauce sweetened
226 gram
200
0
0
50
Weight Watchers Smart 
Ones Ham and Cheese 
Scramble
1 counted pre
180
19
6
13
Ocean Spray Cranberry 
Cocktail Drink, 5.5 fl oz, 48 
Count
2 counted pre
160
0
0
38
Actual
851.7
30.08
15.61
146.01
Goal
850.0
31.9
15.0
146.9
15 g Fat Breakfast 1
15 g Fat Breakfast 2 
Diet Meal Plan B 15 g Fat Breakfast
 
 
 


Clarus Therapeutics, Inc.  
15 September 2016 
CLAR-16015 Version 1.0 
Page 63 of 68 
CONFIDENTIAL 
Meal
Food Description
Amount Measure
Energy Protein Fat
Carbohydrate 
Jimmy Dean Bacon, Egg and 
Cheese Sandwich biscuit 3.6 
oz  
1
counted 
prepackage
330
10
20
27
Belvita Breakfast biscuit 
Nabisco 50g cinnamon 
brown sugar
1
counted 
prepackage
225
4.1
8
35.3
 Chobani non fat fruit yogurt 
(150 gr)
1
counted 
prepackage
120
12
0
19
Milk, chocolate, fluid, 
commercial, lowfat, with 
added vitamin A and vitamin 
D
1 1 cup
177.5
8.1
2.5
31.5
Actual
852.5
34.2
30.5
112.8
Goal
   850.0        31.9     30.0                   113.1 
Thomas 100% Whole Wheat 
Bagel (95gr)
1
counted 
prepackage
240
11
1.5
45
Butter, salted
15 gram
107.55
0.13 12.17
0.01
Egg, whole, cooked, hard‐
boiled
1 1 large
77.5
6.29
5.3
0.56
Bacon, fully cooked, pork (9 
gr/sl) 
30 gram
140.4
10.18 10.53
0.51
Motts Cinnamon Applesauce 
sweetened
1
counted 
prepackage
100
0
0
25
Apple juice, canned or 
bottled, unsweetened
13.5 1 fl oz
192.51
0.42
0.54
47.29
Actual
857.96
28.01 30.04
118.37
Goal
850.0
31.9
30.0
113.1
30 g Fat Breakfast 1
30 g Fat Breakfast 2
Diet Meal Plan C 30 g Fat Breakfast
 
 
 


Clarus Therapeutics, Inc.  
15 September 2016 
CLAR-16015 Version 1.0 
Page 64 of 68 
CONFIDENTIAL 
 
 
Meal
Food Description
Amount Measure
Energy
Protein
Fat
Carbohydrate 
Jimmy Dean sausage Egg 
Cheese croissant
1
counted 
prepackag
e
410
12
28
27
Cheese, mozzarella, part 
skim milk, low moisture
1 1 oz
85.62
7.36
5.68
1.09
Nature Valley Protein 
Chewy Bar
1
counted 
prepackag
e
190
10
12
14
Ocean Spray Cranberry 
Cocktail Drink, 5.5 fl oz, 48 
Count
2
counted 
prepackag
e
160
0
0
38
Actual
845.6
29.4
45.7
80.1
Goal
850.0
31.9
45.0
79.4
Butter, salted
10 gram
71.7
0.09
8.11
0.01
Weight Watchers Smart 
Ones Ham and Cheese 
Scramble
1
counted 
prepackag
e
180
19
6
13
Croissants, butter, large 
(67g)
2
1 croissant, 
large
544.04
10.99
28.14
61.37
Candies, milk chocolate
9.1 gram
48.69
0.7
2.7
5.41
Actual
844.42
30.77
44.95
79.78
Goal
850.0
31.9
45.0
79.4
45 g Fat Breakfast 1
45 g Fat Breakfast 2
Diet Meal Plan D 45 g Fat Breakfast


Clarus Therapeutics, Inc.  
15 September 2016 
CLAR-16015 Version 1.0 
Page 65 of 68 
CONFIDENTIAL 
Meal
Food Description
Amount Measure Energy Protein Fat
Carbohydrate 
Oreida Tater Tots 
(approximately 15 pieces)
140 gram
260.47
3.26 13.02
32.56
Commercially prepared 
sliced bread ( 38 gr/sl) ‐ 
Buttered toast
76 gram
191.52
9.46
2.66
32.46
Butter, salted (used for 
toast and eggs)
20 gram
143.4
0.17 16.22
0.01
Bacon, fully cooked, pork 
(9 gr/sl) 
18 gram
84.24
6.11
6.32
0.31
Egg, whole (fried in butter 
or scrambled with butter 
added)
2 1 large
143
12.56
9.51
0.72
Milk, whole, 3.25% milkfat, 
with added vitamin D
8 1 fl oz
148.84
7.69
7.93
11.71
Actual
971.47
39.24 55.66
77.77
Goal
1000.0
37.5
55.6
87.5
55 g Fat Breakfast ‐ Per FDA Guidelines for Food 
Effect
Diet Meal Plan E (FDA Guideline Meal) 55 g Fat Breakfast
 
 
 


Clarus Therapeutics, Inc.  
15 September 2016 
CLAR-16015 Version 1.0 
Page 66 of 68 
CONFIDENTIAL 
Meal
Food Description
Amount Measure
Energy Protein Fat
Carbohydrate 
amy's bowl brocolli and cheddar 
bake 9.5 oz
1
counted 
prepackage
427
16.5
20.6
44.9
Lays potato chips 1 oz
1
counted 
prepackage
153
1.28 10.07
15
Chobani non fat fruit yogurt (150 
gr)
1
counted 
prepackage
120
12
0
19
Ocean Spray Cranberry Cocktail 
Drink, 5.5 fl oz, 48 Count
1
counted 
prepackage
80
0
0
19
Actual
780
29.78 30.67
97.9
Goal
775.0
29.1
30.0
97.2
amy's bowls mexican casserole 
9.5 oz
1
counted 
prepackage
380
12
16
48
Candies, milk chocolate (Hersey 
Kiss 4.55 gr/kiss)
18.2 gram
97.37
1.39
5.4
10.81
Ocean Spray Cranberry Cocktail 
Drink, 5.5 fl oz, 48 Count
1
counted 
prepackage
80
0
0
19
 Chobani non fat fruit yogurt (150 
gr)
1
counted 
prepackage
120
12
0
19
Cheese, colby
1 1 oz
111.7
6.74
9.1
0.73
Actual
789.07
32.13
30.5
97.54
Goal
775.0
29.1
30.0
97.2
amy's bowl pesto tortellini 9.5 oz
1
counted 
prepackage
440
17
20
50
Applesauce, canned, 
unsweetened 
113 gram
47.46
0.19
0.11
12.74
 Chobani non fat fruit yogurt (150 
gr)
1
counted 
prepackage
120
12
0
19
Lays potato chips 1 oz
1
counted 
prepackage
153
1.28 10.07
15
Actual
760.46
30.47 30.18
96.74
Goal
775.0
29.1
30.0
97.2
Diet Lunch and Dinner Plan for A, B, C, D and E. Subjects may choose any lunch and dinner option listed 
below in any combination.  Subjects must be instructed to consume entire dinner meals.
Lunch  or Dinner Option 1 Total
lunch or Dinner Option 2 Total
Lunch or Dinner Option 3 Total


Clarus Therapeutics, Inc.  
15 September 2016 
CLAR-16015 Version 1.0 
Page 67 of 68 
CONFIDENTIAL 
Meal
Food Description
Amount Measure
Energy Protein Fat
Carbohydrate 
Marie Callender Grilled Chicken 
alfredo bake 369g
1
counted 
prepackage
480
28
21
45
Candies, milk chocolate (Hersey 
Kiss 4.55 gr/kiss)
27.3 gram
146.05
2.09
8.1
16.22
Orange juice, canned, 
unsweetened
10 1 fl oz
146.17
2.11
0.47
34.24
Actual
772.22
32.2 29.56
95.46
Goal
775.0
29.1
30.0
97.2
Lays potato chips 1 oz
1
counted 
prepackage
153
1.28 10.07
15
Nature Valley Protein Chewy Bar
1
counted 
prepackage
190
10
12
14
Apple juice, canned or bottled, 
unsweetened
4 1 fl oz
57.04
0.12
0.16
14.01
Lean Cuisine Craveables Four 
Cheese Pizza
1
counted 
prepackage
380
19
7
60
Actual
780.04
30.4 29.23
103.01
Goal
775.0
29.1
30.0
97.2
Lunch or dinner Option 5Total
Lunch or dinner Option 4 
(no yogurt) Total
 
 
 


Clarus Therapeutics, Inc.  
15 September 2016 
CLAR-16015 Version 1.0 
Page 68 of 68 
CONFIDENTIAL 
Calories
Protein g
Fat  g Carb g
Protein 
calories
Fat 
calories
Carb  
calories
% 
Protein
% fat
% Carb 
2400
90
115 251.25
360
1035
1005
15 43.125 41.875
1000
37.5 55.56
87.5
150
500
350
15
50
35
775
29.1
30.0
97.2
116.3
270.0
388.7
15.0
34.8
50.2
775
29.1
30.0
97.2
116.3
270.0
388.7
15.0
34.8
50.2
Calories
Protein g
Fat g
Carb g
Protein 
calories
Fat  
calories
Carb  
calories
% 
Protein
% fat
% Carb  
2400
90.0 105.0
273.8
360.0
945.0
1095.0
15.0
39.4
45.6
850
31.9
45.0
79.4
127.5
405.0
317.5
15.0
47.6
37.4
775
29.1
30.0
97.2
116.3
270.0
388.8
15.0
34.8
50.2
775
29.1
30.0
97.2
116.3
270.0
388.8
15.0
34.8
50.2
Calories
Protein g
Fat g
Carb g
Protein 
calories
Fat  
calories
Carb  
calories
% 
Protein
% fat
% Carb  
2400
90.0
90.0
307.5
360.0
810.0
1230.0
15.0
33.8
51.3
850
31.9
30.0
113.1
127.5
270.0
452.5
15.0
31.8
53.2
775
29.1
30.0
97.2
116.3
270.0
388.8
15.0
34.8
50.2
775
29.1
30.0
97.2
116.3
270.0
388.8
15.0
34.8
50.2
Calories
Protein g
Fat g
Carb g
Protein 
calories
Fat  
calories
Carb  
calories
% 
Protein
% fat
% Carb  
2400
90.0
75.0
341.3
360.0
675.0
1365.0
15.0
28.1
56.9
850
31.9
15.0
146.9
127.5
135.0
587.5
15.0
15.9
69.1
775
29.1
30.0
97.2
116.3
270.0
388.8
15.0
34.8
50.2
775
29.1
30.0
97.2
116.3
270.0
388.8
15.0
34.8
50.2
Calories
Protein g
Fat g
Carb g
Protein 
calories
Fat  
calories
Carb  
calories
% 
Protein
% fat
% Carb  
2400
90.0
75.0
341.3
360.0
675.0
1365.0
15.0
28.1
56.9
850
31.9
15.0
146.9
127.5
135.0
587.5
15.0
15.9
69.1
775
29.1
30.0
97.2
116.3
270.0
388.8
15.0
34.8
50.2
775
29.1
30.0
97.2
116.3
270.0
388.8
15.0
34.8
50.2
The breakfasts will be defined and contain approximately 850 calories with 15 g fat, 30 g fat, 
or 45 g fat and those meals suggested in the Guidance for Industry on Food‐Effect 
Bioavailability and Fed Bioequivalence Studies (December 2002) namely after an overnight 
fast and with a high‐calorie and high‐fat meal (approximately 1000 calories and 50% of the 
calories from fat). 
FDA High Fat Breakfast (50%; 55 gr) " Meal Plan E"
45 g Fat "Meal Plan D"
30 g Fat "Meal Plan C"
15 g Fat "Meal Plan B"
Fasting "Meal Plan A"
 

SAP_001.pdf: 
Statistical Analysis Plan 
23 March 2017 
Statistical Analysis Plan 
A Phase 2 Study of the Effect of Meals with Various Amounts of Fat Given Immediately 
After Dosing on the Pharmacokinetics of an Oral Testosterone Undecanoate in Hypogonadal 
Men 
Protocol No:  CLAR-16015 
Final Protocol Date:  15 September 2016 
Protocol Amendment 1.0 Date: 08 November 2016 
Compound Name:  Testosterone Undecanoate 
Celerion Project CA20804 
Revised Final Version 
Date:  23 March 2017 
Clarus Therapeutics, Inc. 
555 Skokie Blvd., Suite 340 
Northbrook, IL 60062 
Celerion 
621 Rose Street 
Lincoln, Nebraska 68502 
and 
100 Alexis-Nihon Boulevard, Suite 360, Montreal, Quebec, H4M 2N8, Canada 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 2 of 87 
Safety Statistical Analysis Plan Signature Page 
Clarus Therapeutics, Inc. 
555 Skokie Blvd., Suite Suite 340 
Northbrook, IL 60062 
Compound Name:  Testosterone Undecanoate 
Protocol: 
CLAR-16015 
Study Title: 
A Phase 2 Study of the Effect of Meals with Various Amounts of Fat Given 
Immediately After Dosing on the Pharmacokinetics of an Oral Testosterone 
Undecanoate in Hypogonadal Men 
Issue Date: 
23 March 2017 
Signature:_____________________________________ 
Date:_______________ 
John Brejda, PhD 
Senior Biostatistician I, Data Management and Biometrics 
Celerion 
621 Rose Street 
Lincoln, Nebraska 68502 
Signature:_____________________________________ 
Date:_______________ 
Mohammad Obaidi, PhD 
Senior Scientist, Clinical Pharmacology and Pharmacometrics 
Celerion 
621 Rose Street 
Lincoln, Nebraska 68502 
Signature:_____________________________________ 
Date:_______________ 
Theodore Danoff, MD, PhD 
Chief Medical Officer and Senior Vice President Clinical and Medical Affairs 
Clarus Therapeutics, Inc. 
555 Skokie Blvd, Suite 340 
Northbrook, IL 60062 
                                                                                          


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 3 of 87 
Table of Contents 
1. 
INTRODUCTION .........................................................................................................4 
2. 
OBJECTIVES AND ENDPOINTS ...............................................................................4 
2.1 
Primary Objectives and Endpoints.....................................................................4 
2.2 
Secondary Objectives and Endpoints: ...............................................................5 
3. 
STUDY DESIGN...........................................................................................................6 
4. 
ANALYSIS POPULATIONS .......................................................................................8 
4.1 
Analysis Populations ..........................................................................................8 
4.2 
Preliminary Data and Interim Analysis ..............................................................9 
5. 
TREATMENT DESCRIPTIONS ..................................................................................9 
6. 
PHARMACOKINETIC ANALYSIS ............................................................................9 
6.1 
Measurements and Collection Schedule ............................................................9 
6.2 
Bioanalytical Method .......................................................................................10 
6.3 
Investigational Product and PK Analyte Information ......................................10 
6.4 
Pharmacokinetic Concentrations .....................................................................11 
6.5 
Noncompartmental Pharmacokinetic Analysis and Parameter 
Calculation .......................................................................................................11 
6.6 
Handling of Missing Data and BLQ Values ....................................................13 
6.7 
Data Summarization and Presentation .............................................................14 
6.8 
Statistical Analysis of PK Parameters ..............................................................15 
6.8.1 
Analysis of Variance .........................................................................15 
6.8.2 
Ratios and Confidence Intervals .......................................................15 
6.9 
Secondary Comparisons...................................................................................16 
7. 
SAFETY ......................................................................................................................17 
7.1 
Subject Discontinuation ...................................................................................17 
7.2 
Demographics ..................................................................................................17 
7.3 
Adverse Events ................................................................................................17 
7.4 
Clinical Laboratory Tests .................................................................................18 
7.5 
Vital Signs ........................................................................................................19 
7.6 
Concomitant Medications ................................................................................19 
7.7 
Physical Examination.......................................................................................19 
8. 
SUMMARY TABLES AND FIGURES .....................................................................20 
8.1 
In-text Summary Tables and Figures ...............................................................20 
8.2 
Section 14 Summary Tables and Figures.........................................................22 
8.3 
Section 16 Data Listings ..................................................................................31 
9. 
TABLE SHELLS .........................................................................................................34 
10. 
LISTING SHELLS ......................................................................................................59 
 
 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 4 of 87 
1. INTRODUCTION 
The following analysis plan provides the framework for the summarization of the 
safety and pharmacokinetic data from this study. This document supplements and 
may replace statistical sections appearing in the protocol 
2. OBJECTIVES AND ENDPOINTS 
2.1 
Primary Objectives and Endpoints 
Primary Objectives: 
 
To compare the effect of meals (breakfast) containing various amounts of fat on the 
PK parameters of Clarus's formulation of oral testosterone undecanoate (TU) at a 
dose of 237 mg TU (the highest strength capsule being developed by Clarus). To 
compare maximum A.M. exposure (Cmax-am) and total A.M. exposure (AUCam, 
Cavg-am) of total testosterone (total T) after consuming various lower and higher fat 
content breakfasts and fasting versus 30 g fat for breakfast.  
Primary Endpoints: 
 The following PK parameters for total T will be computed as appropriate: Cmax-am, 
Tmax-am, AUCam, and Cavg-am for the 5 breakfast treatments. 
 The 90% confidence intervals (CIs) of the ratios of least-squares means (LSMs) 
derived from the analyses on the ln-transformed PK parameters Cmax-am, AUCam 
and Cavg-am and will be constructed between the treatment of interest (30 gram fat 
breakfast). The absence of food effect will be concluded if the 90% CIs for the 
ratios of LSMs (Test Treatment/Reference Treatment) derived from the analyses 
of ln-transformed Cmax-am  and AUCam parameters of plasma total T fall within 
80.00% and 125.00%. Presence of a food effect will be concluded if the 90% CIs 
fall outside the range of 70.00% to 143.00%. 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 5 of 87 
2.2 
Secondary Objectives and Endpoints: 
PK Endpoints and Reference Meals for Comparison 
Analyte 
PK Time 
Interval 
PK Endpoint 
Reference Meal 
Total T 
pm 
Tmax-pm*, Cmax-pm, AUCpm, 
Cavg-pm 
30 grams fat 
Total T 
24 
Cmax-24, AUC24, Cavg-24 
30 grams fat 
Total T 
am 
Tmax-am*, Cmax-am, AUCam, 
Cavg-am 
15 grams fat 
Total T 
am 
Tmax-am*, Cmax-am, AUCam, 
Cavg-am 
Fasted 
Total T 
pm 
Tmax-pm*, Cmax-pm, AUCpm, 
Cavg-pm 
Fasted 
Total T 
24 
Cmax-24, AUC24, Cavg-24 
Fasted 
DHT 
am 
Tmax-am*, Cmax-am, AUCam 
30 grams fat 
DHT 
pm 
Tmax-pm*, Cmax-pm, AUCpm 
30 grams fat 
DHT 
24 
Cmax-24, AUC24  
30 grams fat 
TU 
am 
Tmax-am*, Cmax-am, AUCam 
30 grams fat 
TU 
pm 
Tmax-pm*, Cmax-pm, AUCpm 
30 grams fat 
TU 
24 
Cmax-24, AUC24 
30 grams fat 
* will not be used in the statistical comparisons 
 
 The 90% CIs of the ratios of LSMs derived from the analyses on the 
ln-transformed PK parameters Cmax-am, Cmax-pm, Cmax24, AUCam, AUCpm, AUC24, 
Cavg-am, Cavg-pm, and Cavg-24 for Total T, DHT(Cmax and AUC only), and TU(Cmax 
and AUC only) will be constructed between the treatments of interest.  
 
 Comparisons between treatments for the above secondary endpoints will be made 
using the ratios of the LSMs derived from ANOVA of the ln-transformed PK 
parameters (except for the various Tmax metrics) for plasma Total T using 30 g fat 
and 15 g fat breakfast meals as references.  
Safety Objective and Endpoints: 
To characterize the safety and tolerability of oral TU when consumed with various 
meals. 
Safety endpoints are incidence of treatment emergent adverse events. Other key 
safety endpoints are change in physical examination findings, change in vital sign 
measurements, and change in relevant clinical laboratory tests (e.g., hematocrit).  


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 6 of 87 
3. STUDY DESIGN 
This is a multicenter, Phase 2, repeated, twice daily dose, food effect study in which 
subjects are randomized to a sequence of meals that vary primarily in fat content (see 
Tables 3.1 and 3.2 below). Approximately 20 hypogonadal subjects will be enrolled 
in order to complete approximately 16 subjects. Subjects may be naïve to androgen 
replacement therapy or washed out of prior androgen replacement therapies as 
detailed in exclusion criteria. 
There will be a Run-In Phase (twice daily dosing with meals) designed to suppress 
subjects’ endogenous testosterone production while allowing the oral TU to reach 
steady state followed by a PK Phase. Throughout the study, the dose of study drug 
will be 237 mg TU twice daily, which is the highest strength formulation in 
development and the starting dose for the ongoing Phase 3 study, CLAR-15012. 
After the 14 day Run-In Phase, subjects will be confined in the clinic for 
approximately 6 consecutive days for evaluations and serial blood draws in the PK 
Phase. Subjects will present at the clinic on the evening of Day 14 prior to dinner 
time and will be dosed with oral TU immediately prior to a dinner meal. They will 
remain in the clinic until collection of 24-hour serial sampling following morning 
dosing in Period 5 of the PK Phase. On each of the PK Phase Periods 1 through 5, the 
subject will be dosed immediately prior to the breakfast meal (or in the AM with 240 
mL of water for the fasting period). The breakfasts will be defined and contain 
approximately 850 calories with 15 g fat, 30 g fat, or 45 g fat and those meals 
suggested in the Guidance for Industry on Food-Effect Bioavailability and Fed 
Bioequivalence Studies (December 2002), namely after an overnight fast or with a 
high-calorie and high-fat meal (approximately 1000 calories and 50% of the calories 
from fat). The 15 g, 30 g, and 45 g fat meals are meal options that are incorporated 
into the ongoing Phase 3 study. Subjects will be randomized to a sequence of the five 
defined meal plans (including fasting) to be administered on PK Phase Periods 1 
through 5 (Days 1 through 5).  
Table 3.1 Meals Plans Provided During the PK Phase  
Meal Plan A (Fasting) 
Overnight fast (≥10 hours) 
Dose oral TU with 240 mL of water 
Fast additional 4 hours 
Lunch 30 grams fat 
Dinner 30 grams fat 
Meal Plan B (15 gm fat) 
Overnight fast (≥10 hours) 
Dose oral TU immediately prior to 
breakfast 
Breakfast 15 grams fat 
Lunch 30 grams fat 
Dinner 30 grams fat 
Meal Plan C (30 gm fat, Reference 
Meal) 
Overnight fast (≥10 hours) 
Dose oral TU immediately prior to 
breakfast 
Meal Plan D (45 gm fat) 
Overnight fast (≥10 hours) 
Dose oral TU immediately prior to 
breakfast 
Breakfast 45 grams fat 


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Breakfast 30 grams fat 
Lunch 30 grams fat 
Dinner 30 grams fat 
Lunch 30 grams fat 
Dinner 30 grams fat 
Meal Plan E (FDA high-calorie high-
fat) 
Overnight fast (≥10 hours) 
Dose oral TU immediately prior to 
breakfast 
Breakfast FDA high-fat, high-calorie 
meal 
(≈1000 calories, 50% of calories as fat) 
Lunch 30 grams fat 
Dinner 30 grams fat 
 
 
 
 


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Table 3.2 Subject Sequence Assignments 
 
Period 1 
Period 2 
Period 3 
Period 4 
Period 5 
Sequence 1 
A 
B 
C 
D 
E 
Sequence 2 
B 
C 
E 
A 
D 
Sequence 3 
C 
E 
D 
B 
A 
Sequence 4 
D 
A 
B 
E 
C 
Sequence 5 
E 
D 
A 
C 
B 
The confinement for the PK Phase will begin immediately prior to the evening dose 
and meal on Run-In Day 14, and will continue through collection of a blood sample 
24 hours after the morning dose of the fifth dosing period (Period 5) for a total of 
approximately 135 hours. During the PK Phase, subjects will have all meals provided, 
will undergo observed dosing (dosing of study medication taken from site inventory 
will be observed by site personnel), will have blood samples collected and will have 
limited activity. During this phase, the subjects must consume their entire breakfast 
and dinner meals and study drug will be administered in the morning and evening 
(approximately 12 hours apart) immediately before breakfast and dinner. 
For all subjects, serial blood samples will be collected as follows: 0 (pre-morning 
dose), 2, 4, 6, 9, 12, 14, 16, 18, 21, and 24 hours after the morning dose. Blood 
sample collection should be performed within ± 10 minutes of the scheduled time 
points (with the exception of the 0-hour time point which should be performed no 
more than 5 minutes before oral TU dose administration on each PK Phase Period). 
The 24-hour PK blood sample on a just completed PK Phase period (Day 1, 2, 3 or 4) 
will also serve as the predose blood sample for the immediately following morning 
dose (Day 2, 3, 4 or 5, respectively). 
Subjects will be released from the clinic following the 24-hour blood draw and 
designated end of study activities of the PK Phase, which occurs the morning after the 
fifth PK Phase study period. 
Each subject will participate in the study for approximately 8 weeks, including up to a 
28-day Screening Phase, a 14-day out-patient Run-In Phase, and a 6-day in-patient 
PK Phase, followed by a 5 to 7 day Safety Follow–up Phase to assess safety. 
4. ANALYSIS POPULATIONS 
4.1 
Analysis Populations 
PK Population: The PK population shall consist of all subjects in the study who have 
at least 1 evaluable PK profile (calculable Cmax-am and Cavg-am) and no significant 
protocol deviations. 
PK Evaluable Population: All subjects in the PK population who comply sufficiently 
with the protocol and display an evaluable PK profile (e.g., exposure to treatment, 


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availability of measurements, and absence of major protocol violations). PK 
evaluable population will be used in the PK parameter summary and statistical 
analyses. Food effect assessment will be conducted only on data from subjects who 
complete the study or have sufficient data for a pairwise comparison (i.e. have at 
completed at least 2 periods, 1 of which must be for Treatment C [30 g fat] or 
Treatment B [15 g fat], which serve as the reference meals for the primary and 
secondary comparisons, respectively). 
A sensitivity analysis will also be performed on a sub-set of subjects, to be 
determined by Clarus that will exclude subjects who were determined to not have 
eaten the majority of the fat containing food in their meal. 
Safety Population: All subjects who received at least one dose of the study drug. 
Safety population will be used in the safety summarizations. 
4.2 
Preliminary Data and Interim Analysis 
No interim analysis is planned for the study.  
5. TREATMENT DESCRIPTIONS 
Treatments A, B, C, D and E are described as follows: 
Treatment A: 237 mg TU Administered BID Under Fasting Condition for Breakfast 
Treatment B: 237 mg TU Administered BID with 15 g fat Breakfast 
Treatment C: 237 mg TU Administered BID with 30 g fat Breakfast 
Treatment D: 237 mg TU Administered BID with 45 g fat Breakfast 
Treatment E: 237 mg TU Administered BID with FDA High-Calorie, High-fat 
Breakfast 
 
In each treatment arm, the second oral TU dose of the day is administered 
immediately prior to a dinner containing 30 g fat. 
Additional details of each treatment can be found in Table 3.1, Section 3. 
6. PHARMACOKINETIC ANALYSIS 
Note: PK parameters will not be calculated by Celerion. However, Celerion will 
complete the statistical analyses of PK parameters and provide the PK tables, listings 
and figures.  
6.1 
Measurements and Collection Schedule 
Serial blood samples will be collected for total T, dihydrotestosterone (DHT) and TU 
concentration determinations, for Periods 1 through 5, according to the following 
schedule: 0 (pre-morning dose), 2, 4, 6, 9, 12, 14, 16, 18, 21 and 24 hours after the 


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morning dose. The 24 hours sample on Days 1-4 serve as the 0 (pre-morning dose) 
samples for Days 2-5. 
Note: For calculating the PK parameters, the 12-hour time point will be used as the 
last time point for AM dose and as the predose time point for the PM dose. 
Concentrations for total T, DHT and TU will be included in the individual 
concentration-time plots (based on actual sample times), as well as in the mean 
concentration-time plots (based on nominal sample times); however, if there are any 
significant sampling time deviations, additional concentration-time plots of the mean 
data may be provided. 
6.2 
Bioanalytical Method 
Total T and DHT  
Plasma concentrations of total T and DHT will be determined in human NaF+EDTA 
plasma using liquid-chromatography and tandem-mass spectrometry (LC/MS/MS), as 
validated at inVentiv Health Clinique, Quebec, Canada. The lower limit of 
quantitation (LLOQ) for total T and DHT are 10 ng/dL and 5 ng/dL, respectively.  
TU 
Plasma concentrations of total TU will be determined in human NaF+EDTA plasma 
using LC/MS/MS as validated at the Los Angeles Biomedical Research Institute (LA 
Biomed), Torrance, California. The lower limit of quantitation (LLOQ) for TU is 
2 ng/mL.  
6.3 
Investigational Product and PK Analyte Information 
Testosterone undecanoate (TU) is currently being developed for the treatment of 
hypogonadism.   
The chemical characteristics of TU are presented below: 
Chemical Name:  
17β-undecanoyloxy-androst-4-en-3-one CAS: 549-44-0 
Molecular Formula:  
C30H48O3 
Molecular Weight:  
456.7 g/mol  


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Chemical structure:  
 
Clarus’s formulation of oral TU at a dose of 237 mg TU (the highest strength capsule 
being developed by Clarus) contains 150 mg T per capsule. 
TU is the undecanoate ester of T. T has a molecular weight of 288.42 g/mol and 
a molecular formula C19H28O2. Its metabolite DHT has a molecular weight of 
290.44 g/mol and a molecular formula C19H30O2. Their molecular structures are 
shown in the following figures: 
 
 
 
 
 
 
 
 
 
 
Testosterone  
 
 
 
 
 
Dihydrotestosterone 
 
 
6.4 
Pharmacokinetic Concentrations 
Plasma concentrations of total T, DHT and TU collected at the times described in 
Section 6.1, and using the bioanalytical methods described in Section 6.2, will be 
used for the calculation of the plasma total T, DHT and TU PK parameters, 
respectively.  Only total T PK parameters will be compared using a statistical model 
for assessment of food effects. 
6.5 
Noncompartmental Pharmacokinetic Analysis and Parameter Calculation 
The appropriate noncompartmental, model-independent PK parameters will be 
calculated from the plasma total T, DHT, and TU concentration-time data using 
Microsoft® Excel® 2013. All PK parameters included in the protocol are listed in 
Table 6.1, and are defined as appropriate for study design. 


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Table 6.1 Noncompartmental Plasma Pharmacokinetic Parameters to be 
Calculated  
Parameter 
Definition 
Method of Determination 
AUCam 
 
Area under the concentration-
time curve over the morning 
dosing interval 
Calculated using the linear 
trapezoidal method  
AUCpm 
 
Area under the concentration-
time curve over the evening 
dosing interval 
Calculated using the linear 
trapezoidal method  
AUC24 
Area under the concentration-
time curve over the combined 
morning and evening dosing 
intervals 
Calculated using the linear 
trapezoidal method 
Cmax-am  
Maximum measured plasma 
concentration following the 
morning dose  
Taken directly from the 
bioanalytical data 
Cmax-pm 
Maximum measured plasma 
concentration following the 
evening dose  
Taken directly from the 
bioanalytical data 
Cmax-24 
Maximum measured plasma 
concentration over the combined 
morning and evening dosing 
intervals 
Taken directly from the 
bioanalytical data 
Tmax-am  
Time to reach Cmax-am. If the 
maximum value occurs at more 
than one time point, Tmax-am is 
defined as the first time point 
with this value  
Taken directly from the 
bioanalytical data 
Tmax-pm 
Time to reach Cmax-pm. If the 
maximum value occurs at more 
than one time point, Tmax-pm is 
defined as the first time point 
with this value  
Taken directly from the 
bioanalytical data 
Cavg-am 
Time-weighted average plasma 
concentration over the dosing 
interval following the morning 
dose 

AUCam
am
Cavg
 
 

 
where τ is the anticipated 
dosing interval for the clinic. 


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Parameter 
Definition 
Method of Determination 
Cavg-pm 
Time-weighted average plasma 
concentration over the dosing 
interval following the evening 
dose 

AUCpm
pm
Cavg
 
 

 
where τ is the anticipated 
dosing interval for the clinic. 
Cavg-24 
Time-weighted average plasma 
concentration over the combined 
period of the morning and 
evening dosing intervals.  
24
24
 
 
24
AUC
Cavg

 
Additional PK parameters may be computed if deemed appropriate for meeting the 
objectives of the study. 
The primary comparisons of interest will be the total T exposure (maximum and 
cumulative) over the dosing interval following the morning doses of TU for each 
specific treatment period.   
When sufficient concentration data exist, the analogous PK parameters (AUCpm, 
Cmax-pm, Tmax-pm, and Cavg-pm) for total T will be calculated following the evening dose 
of TU, and the analogous PK parameters (Cmax-24, AUC24, and Cavg-24) for the 
combined 24-hour period (following both the morning and evening doses of TU for 
each specific treatment period).  In addition, the morning dose, evening dose, and full 
day PK parameter versions of Cmax, Tmax, and AUC will be calculated for DHT and 
TU following the doses of TU for each treatment period. Note that Tmax will not be 
calculated for the full day. 
As the treatment doses will be administered while endogenous T production has been 
suppressed, the total T values will not be corrected for baseline T concentrations. 
Actual sample times will be used in the calculation of PK parameters. If a measurement 
value is available but the actual time is not captured, the time will be replaced with the 
nominal time for that visit. Subjects for whom there are insufficient data to calculate 
PK parameters for an analyte will be included in the concentration tables only and 
excluded from the statistical analysis of that analyte.  
6.6 
Handling of Missing Data and BLQ Values 
Calculation of PK parameters  
For noncompartmental PK parameter calculations, missing concentrations will not be 
imputed, except when estimation from existing data is supported by standard PK 
principals as detailed below. A missing concentration value adjacent to the existing 
Cmax will make a subject non-evaluable for Cmax, Tmax, and AUC calculations. If more 
than one concentration in sequence is missing, the subject will be considered 


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non-evaluable for AUCs, unless the missing concentrations are embedded in a series 
of assay results that are below the limit of quantitation (BLQ). 
 Single embedded missing concentrations will be treated as missing and the 
affected AUCs calculated, if appropriate based on PK principals, by extending the 
trapezoid to the next existing concentration.  
 Missing actual sample collection times may be replaced with nominal scheduled 
sample collection times based on case-by-case review.  
 Leading, trailing and embedded BLQ values will be treated as one-half the lower 
limit of quantitation (LLOQ/2) for total T and DHT, but as zero (0.0) for TU since 
TU is not an endogenous molecule.  
 A missing predose concentrations (i.e., at T=0 or T=24) may be replaced by a 
value equal to the morning dose concentration of the preceding or following PK 
Phase treatment.  
 A missing predose concentration prior to the evening TU dose may be estimated 
by linear or log-linear extrapolation, as appropriate, of the 6 and 9-hour samples if 
that process is consistent with the observed PK pattern for other subjects when 
receiving the same treatment. 
 
Summary Statistics 
For the calculation of total T and DHT concentration summary statistics, values that 
are BLQ will be treated as LLOQ/2. For the calculations of TU concentration 
summary statistics, values that are BLQ will be treated as ‘0’ (zero). 
 
6.7 
Data Summarization and Presentation 
All total T, DHT and TU PK concentrations and PK parameter descriptive statistics 
will be generated using SAS® Version 9.3. 
For all subjects in the PK Population, plasma total T, DHT and TU concentrations 
will be listed by subject, and summary statistics, including number of observations 
(n), arithmetic mean (Mean), standard deviation (SD), coefficient of variation (CV%), 
standard error of the mean (SEM), minimum, median, and maximum, will be 
calculated by nominal time point for each treatment separately. Data from excluded 
subjects will be listed but excluded from the summary statistics and noted as such in 
the tables. All BLQ values will be presented as “BLQ” in the concentration table 
listings and footnoted accordingly.  
Plasma total T, DHT and TU PK parameters will be listed and summary statistics will 
be calculated for each treatment separately in the PK Evaluable Population. Summary 
statistics will include: n, Mean, SD, CV, SEM, minimum, median, maximum, 
geometric mean (Geom Mean), and geometric CV% (Geom CV%).  
Data from excluded subjects will be listed but excluded from the summary statistics 
and statistical analysis and noted as such in the tables.  


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The level of precision for each statistic will be presented as follows:   
 minimum/maximum in same precision as in bioanalytical data (the 
bioanalytical data will be rounded to 3 significant figures) or parameter 
output, 
 Mean/median/Geom Mean in one more level of precision than 
minimum/maximum, 
 SD and SEM in one more level of precision than Mean/median, 
 CV% and Geom CV% will be presented to 1 decimal place, 
 n will be presented as an integer (no decimal place). 
Mean (based on nominal time) and individual (based on actual time) concentration 
time profiles will be presented on linear and semi-log scales for plasma total T, DHT 
and TU concentrations as appropriate. Linear mean plots will be presented with and 
without SD.   
6.8 
Statistical Analysis of PK Parameters  
6.8.1 Analysis of Variance 
An analysis of variance (ANOVA) will be performed on the natural log 
(ln)-transformed Cmax-am, AUCam, and Cavg-am . The ANOVA model will include 
treatment received, sequence, and period as fixed-effects, and subject nested within 
sequence as a random-effect. A sequence effects will be estimated by testing 
sequence using subject nested within sequence as the error term at a 10% level of 
significance. Each ANOVA will include calculation of treatment LSMs as well as the 
difference between treatment LSMs. The statistical analyses will be done using the 
following example SAS® code. 
PROC MIXED; 
CLASS Sequence Subject Treatment Period; 
MODEL PK_Parameter = Sequence Treatment Period / DDFM=KR; 
RANDOM Subject(Sequence); 
ESTIMATE “Fasting (A) vs 30 g fat (C)” Treatment 1 0 -1 0 0/CL ALPHA=0.1 E; 
ESTIMATE “15 g fat (B) vs 30 g fat (C)” Treatment 0 1 -1 0 0/CL ALPHA=0.1 E; 
ESTIMATE “45 g fat (D) vs 30 g fat (C)” Treatment 0 0 -1 1 0/CL ALPHA=0.1 E; 
ESTIMATE “high-fat (E) vs 30 g fat (C)” Treatment 0 0 -1 0 1/CL ALPHA=0.1 E; 
LSMEANS Treatment/CL; 
RUN; 
 
6.8.2 Ratios and Confidence Intervals 
For the primary comparisons two-way contrasts will be made using the 30 g fat meal 
as the reference treatment, and the point estimate and 90% CI for the LSM mean 


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difference in ln-transformed PK parameters Cmax-am, AUCam, and Cavg-am will be 
exponentiated to obtain estimates for ratios of geometric LSMs on the original scale. 
No food effect will be concluded for a contrasted treatment if the 90% CI about the 
ratio of geometric LSMs of Cmax-am and AUCam for that contrast lie totally within the 
0.80 to 1.25 interval. Presence of a food effect will be concluded if the 90% CIs fall 
outside the range of 70.00% to 143.00%. 
6.9 
Secondary Comparisons 
In addition to the primary comparisons as described in Section 6.7, secondary 
comparisons will be made for total T for Cmax-pm, AUCpm, Cmax24, and AUC24. 
Secondary comparisons with the 15 g fat meal (B) versus the other treatments, and 
the fasting treatment (A) versus other treatments will be provided to identify the 
effect of meal type on Cmax-am, AUCam, and Cavg-am for total T. The following estimate 
statements will be used with the ANOVA model to calculate the treatment differences 
for the secondary comparisons (statistical testing will not be completed for fasting 
comparisons): 
 
Secondary Comparisons: 
 
ESTIMATE “Fasting (A) vs 15 g fat (B)”  Treatment 1 -1 0 0 0/CL ALPHA=0.1 E; 
ESTIMATE “30 g fat (C) vs 15 g fat (B)” Treatment 0 -1 1 0 0/CL ALPHA=0.1 E; 
ESTIMATE “45 g fat (D) vs 15 g fat (B)” Treatment 0 -1 0 1 0/CL ALPHA=0.1 E; 
ESTIMATE “high-fat (E) vs 15 g fat (B)” Treatment 0 -1 0 0 1/CL ALPHA=0.1 E; 
 
ESTIMATE “15 g fat (B) vs Fasting (A)” Treatment -1 1 0 0 0/E; 
ESTIMATE “30 g fat (C) vs Fasting (A)” Treatment -1 0 1 0 0/E; 
ESTIMATE “45 g fat (D) vs Fasting (A)” Treatment -1 0 0 1 0/E; 
ESTIMATE “high-fat (E) vs Fasting (A)” Treatment -1 0 0 0 1/E; 
 
Ratios of geometric LSMs will be calculated using the exponentiation of the 
difference between treatment LSM from the analyses on the ln-transformed Cmax-am, 
AUCam, and Cavg-am. These ratios will be expressed as a percentage relative to the 
fasting condition, i.e. the reference treatment (Treatments B and A respectively). CIs 
will not be calculated for the comparisons with the fasting treatment (A). 
Sensitivity Analysis: 
A sensitivity analysis will be performed using the same comparisons defined for the 
primary analysis but with a subset of subjects, determined by Clarus, that exclude 
subjects who were determined to not have eaten the majority of the fat containing 
food in their meal. 


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7. SAFETY  
All clinical safety and tolerability data will be listed by subject and assessment time 
points, including rechecks, unscheduled assessments, and early termination, 
chronologically.  
Continuous safety variables will be summarized using n, arithmetic mean, SD, 
minimum, median and maximum. Frequency counts will be reported for categorical 
data when appropriate.  
The level of precision for the descriptive statistics will be presented as follows: 
minimum/maximum in same precision as in the database, mean/median in one more 
precision level than minimum/maximum, SD in one more precision level than 
mean/median, and n will be presented as an integer. 
Where individual data points are missing because of dropouts or other reasons, the 
data will be summarized based on reduced denominators. 
No inferential statistics are to be performed on safety endpoints. 
7.1 
Subject Discontinuation 
Subjects will be summarized by number of subjects enrolled and randomized, dosed, 
completed, and discontinued the study. These tabulations include the number of 
subjects discontinuation by reason specified for discontinuation. In addition, a table 
presenting dosing status of each subject by treatment will be created.   
7.2 
Demographics 
Descriptive statistics will be calculated for continuous variables (age, weight, height, 
body mass index [BMI], prostate specific antigen [PSA] International Prostate 
Symptom Score [I-PSS], and Quality of Life Due to Urinary Symptoms Score). Age 
will be calculated in years between date of birth and date of informed consent. 
Frequency counts and corresponding percentages will be provided for categorical 
variables (gender, race and ethnicity). 
7.3 
Adverse Events 
All adverse events (AEs) occurring during this clinical trial will be coded using the 
Medical Dictionary for Regulatory Activities (MedDRA®), Version 15.1.   
All AEs captured in the database will be listed in by-subject data listings including 
verbatim term, coded term, treatment, frequency, severity, serious, outcome, action 
taken and relationship to study medication. However, only treatment-emergent AEs 
(TEAEs) will be summarized. AEs that occur during the Run-In Phase will be 
considered to be treatment-emergent. 


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An AE is considered treatment-emergent if it begins or worsens in severity after the 
first dose of the study drug. If an AE increases in severity, that AE will be given a 
resolution date and time and a new record will be initiated with the new severity. If 
the severity of an AE remains the same or decreases, the AE will be kept open 
through to resolution and the maximum severity will be recorded.  
The number and percentage of subjects with TEAEs will be tabulated by System 
Organ Class (SOC) and Preferred Term. Summary tables will include number of 
subjects reporting the AE and as percent of number of subjects dosed, by Phase (Run-
In and PK and Follow-Up). Number of TEAEs will be summarized in a similar 
manner. A summary of the number of subjects with TEAEs will be provided by 
severity and by relationship to study drug. If for any AE severity and/or relationship 
to drug is missing, then the least favorable choice(s) (Severe and Definitely) will be 
assigned for purposes of tabulation and listing. Subjects reporting more than 1 AE for 
a given MedDRA® preferred term will be counted only once for that term using the 
most severe incident. Subjects reporting more than 1 type of event within an SOC 
will be counted only once for that SOC. Incidence of TEAEs, serious TEAEs, TEAEs 
resulting in discontinuation from study drug, and TEAEs resulting in death will be 
summarized. Listings will be provided for all AEs, SAEs, and AEs resulting in 
treatment discontinuation.   
7.4 
Clinical Laboratory Tests  
Blood samples for the clinical safety laboratory tests, including PSA, will be collected 
at Screening 1, Run-In Phase Day 1, PK Phase Day 1, following the 24-hour PK 
blood draw on PK Phase Day 6, and 5 to 7 days post last dose during the Safety 
Follow-Up Phase, if the subject needed to return to the clinic for an in person visit, or 
at Early Termination from the study. Samples for safety lab tests will be collected in 
the morning after obtaining vital signs and after overnight fasting, but before meals 
and study drug administration. Urinalysis will only be assessed at Screening 1. 
All out-of-range values for serum chemistry, hematology and urinalysis will be listed 
by subject. Out-of-range values are considered to be values that are out-of- normal 
range as defined by the clinical laboratory. The normal range values will be displayed 
in the data listings along with the Principal Investigator’s (PI’s) interpretation.   
For all serum chemistry and hematology safety laboratory values (including PSA 
results) that are numeric, descriptive statistics will be presented for each laboratory 
test by assessment time point. Change from baseline will be summarized in a similar 
manner. The test results from Screening 1 will serve as the baseline for change from 
baseline calculations. Rechecks, unscheduled assessments and early termination 
measurements taken after first dosing will not be used in the summarization. Subjects 
will only return for clinical lab assessment during the Safety Follow-up Phase if there 
is a specific need. Therefore, clinical labs will not be summarized for the Safety 
Follow-up visit. Urinalysis is only assessed at Screening 1. Therefore, change from 
baseline will not be calculated for urinalysis. 


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Serum total testosterone assessed at Screening 1 and Screening 2, and DHT assessed 
at Run-In Phase Day 1 will be listed but not summarized. 
7.5 
Vital Signs 
Vital signs, including systolic and diastolic blood pressure and heart rate will be 
measured in triplicate at Screening 1, Run-In Phase Day 1, and prior to dosing during 
the PK Phase on Days 1, 2, 3, 4, 5, and 6, and 5 to 7 days post last dose during the 
Safety Follow-Up Phase, if a clinical visit is required for the safety follow up, or at 
Early Termination. The subject should be sitting at rest for at least 5 minutes with his 
feet resting on the floor and before BP and HR are measured 3 times at 1 to 2 minute 
intervals. Respiration rate and temperature are only collected during Screening 1 and 
at Early Termination. 
Descriptive statistics (n, mean, SD, median, minimum, and maximum) will be 
provided for vital sign variables systolic and diastolic blood pressure and heart rate at 
each assessment time point, including change from baseline.  The mean of the 
triplicate values will be used in the calculation of the summary statistics. The vital 
signs measurements on Day 1 of the Run-In Phase will serve as the baseline for 
calculating change from baseline. Rechecks, unscheduled assessments and early 
termination measurements taken after initial study dosing will not be used in the 
summarization. Subjects will only return for vital signs assessment during the Safety 
Follow-up Phase if there is a specific need. Therefore, vital signs will not be 
summarized for the Safety Follow-up visit. Respiration rate and temperature are only 
collected at Screening 1 and Early Termination. Therefore, change from baseline will 
not be calculated for these measurements. 
Vital signs will also be displayed in a data listing by subject. 
7.6 
Concomitant Medications 
All prior and concomitant medications recorded during the study will be coded with 
the WHO Dictionary Version September 2012 and listed. Prior medications are 
defined as medications documented on the Prior and Concomitant Medications 
CRF/eCRF as having started and stopped before the first dose of any study drug. 
Concomitant medications are defined as medications documented on the Prior and 
Concomitant Medications CRF/eCRF as having started after the start of study drug or 
having started before the start of study drug and continued on or after the first dose of 
any study drug. Prior and concomitant medications will be summarized by WHO 
term in separate tables. All concomitant medications administered will be tabulated in 
a data listing. 
7.7 
Physical Examination 
A complete physical examination (PE) with a digital rectal examination (DRE) will 
be performed at Screening 2. A PE may also be completed 5 to 7 days post last dose 


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during the Safety Follow-Up Phase if needed, or at Early Termination. A brief PE 
without DRE will be performed on Day 1 prior to dosing during the 14 Day Run-In 
Phase and prior to departing the clinic following the last PK Phase. For all subjects, a 
symptom-directed physical examination will be performed when necessary. Any 
relevant findings from the PI during screening will be reported as medical history. 
Any significant PE findings after dosing will be recorded as AEs. A by-subject listing 
will be provided.   
8. SUMMARY TABLES AND FIGURES 
Summary tables and figures are numbered following the ICH structure but may be 
renumbered as appropriate during the compilation of the tables and figures for the 
report. Please note that all safety summary tables will be generated using SAS®.  
The following are lists of TFLs numbers and titles that will be included within the 
report.  
8.1 
In-text Summary Tables and Figures 
The following is a list of table and figure titles that will be included in the text of the 
report. Tables and figures will be numbered appropriately during compilation of the 
report. 
Section 10: 
Table 10-1 
Disposition Summary 
Table 10-2 
Demographic Summary  
Section 11: 
Tables: 
Primary PK Parameters for Total T (Cmax-am, Tmax-am, AUCam, and Cavg-am) and 
Secondary PK Parameters for Total T (Cmax-pm, Tmax-pm, AUCpm, 
Cavg-pm, Cmax-24, AUC24, and Cavg-24) 
Table 11-1 
Summary of Plasma Total T Pharmacokinetic Parameters Following 
Treatments A, B, C, D, and E (PK Evaluable Population) 
Primary PK Comparison for Total T (Cmax-am, AUCam, and Cavg-am)  
Table 11-2 
Primary Statistical Comparisons of Plasma Total T Pharmacokinetic 
Parameters Following Treatments A, B, D, and E Versus Treatment C 
(PK Evaluable Population) 
Secondary PK Comparison for Total T (Cmax-am, AUCam, and Cavg-am)  
Table 11-3 
Secondary Statistical Comparisons of Plasma Total T Pharmacokinetic 
Parameters Following Treatments A, C, D, and E Versus Treatment B 


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(PK Evaluable Population) 
Table 11-4 
Secondary Statistical Comparisons of Plasma Total T Pharmacokinetic 
Parameters Following Treatments B, C, D, and E Versus Treatment A 
(PK Evaluable Population) 
Secondary PK Comparison for Total T (Cmax-pm, AUCpm, Cavg-pm, Cmax-24, AUC24, 
and Cavg-24)  
Table 11-5 
Secondary Statistical Comparisons of Plasma Total T Pharmacokinetic 
Parameters Following Treatments A, B, D, and E Versus Treatment C 
(PK Evaluable Population) 
Table 11-6 
Secondary Statistical Comparisons of Plasma Total T Pharmacokinetic 
Parameters Following Treatments B, C, D, and E Versus Treatment A 
(PK Evaluable Population) 
Secondary PK Parameters for DHT (Cmax-am, Tmax-am, AUCam, Cmax-pm, Tmax-pm, 
AUCpm, Cmax-24, and AUC24) 
Table 11-7 
Summary of Plasma DHT Pharmacokinetic Parameters Following 
Treatments A, B, C, D, and E (PK Evaluable Population) 
Secondary PK Comparisons for DHT (Cmax-am, AUCam, Cmax-pm, AUCpm, 
Cmax-24, and AUC24) 
Table 11-8 
Secondary Statistical Comparisons of Plasma DHT Pharmacokinetic 
Parameters Following Treatments A, B, D, and E Versus Treatment C 
(PK Evaluable Population) 
Secondary PK Parameters for TU (Cmax-am, Tmax-am, AUCam, Cmax-pm, Tmax-pm, 
AUCpm, Cmax-24, and AUC24) 
Table 11-9 
Summary of Plasma TU Pharmacokinetic Parameters Following 
Treatments A, B, C, D, and E (PK Evaluable Population) 
Secondary PK Comparisons for TU (Cmax-am, AUCam, Cmax-pm, AUCpm, Cmax-24, 
and AUC24) 
Table 11-10 
Secondary Statistical Comparisons of Plasma TU Pharmacokinetic 
Parameters Following Treatments A, B, D, and E Versus Treatment C 
(PK Evaluable Population) 
Figures: 
Figure 11-1 
Arithmetic Mean Plasma Total T Concentration-Time Profiles 
Following Treatments A, B, C, D, and E (PK Evaluable Population) 
Figure 11-2 
Arithmetic Mean Plasma DHT Concentration-Time Profiles Following 
Treatments A, B, C, D, and E (PK Evaluable Population) 
Figure 11-3 
Arithmetic Mean Plasma TU Concentration-Time Profiles Following 
Treatments A, B, C, D, and E (PK Evaluable Population) 


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Sensitivity analysis: 
Primary PK Parameters (Cmax-am, AUCam, and Cavg-am)  
Table 11-11 
Statistical Comparisons of Plasma Total T Pharmacokinetic 
Parameters Following Treatments A, B, D, and E Versus Treatment C 
(A Sub-set of PK Evaluable Population) 
 
Section 12: 
Table 12-1 
Incidence of Treatment-Emergent Adverse Events by Phase 
8.2 
Section 14 Summary Tables and Figures 
The following is a list of table and figure titles that will be included in Section 14 of 
the CSR. 
14.1 
Demographic Data Summary Tables  
Table 14.1.1 Summary of Disposition 
Table 14.1.2 Disposition of Subjects 
Table 14.1.3 Demographic Summary 
14.2 
Pharmacokinetic Data Summary Tables and Figures  
14.2.1 
Tables 
14.2.1.1 Concentration Tables 
 
Total T 
Table 14.2.1.1.1 
Plasma Total T Concentrations (ng/dL) Following  
Administration of 237 mg TU BID Under Fasting Condition 
for Breakfast (Treatment A) (PK Population) 
Table 14.2.1.1.2 
Plasma Total T Concentrations (ng/dL) Following 
Administration of 237 mg TU BID with 15 g fat Breakfast 
(Treatment B) (PK Population) 
Table 14.2.1.1.3 
Plasma Total T Concentrations (ng/dL) Following 
Administration of 237 mg TU BID with 30 g fat Breakfast 
(Treatment C) (PK Population) 
Table 14.2.1.1.4 
Plasma Total T Concentrations (ng/dL) Following 
Administration of 237 mg TU BID with 45 g fat Breakfast 
(Treatment D) (PK Population) 


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Table 14.2.1.1.5 
Plasma Total T Concentrations (ng/dL) Following 
Administration of 237 mg TU BID with FDA High-Calorie 
High-fat Breakfast (Treatment E) (PK Population) 
DHT 
 
Table 14.2.1.1.6 
Plasma DHT Concentrations (ng/dL) Following 
Administration of 237 mg TU BID Under Fasting Condition 
for Breakfast  (Treatment A) (PK Population) 
Table 14.2.1.1.7 
Plasma DHT Concentrations (ng/dL) Following 
Administration of 237 mg TU BID with 15 g fat Breakfast 
(Treatment B) (PK Population) 
Table 14.2.1.1.8 
Plasma DHT Concentrations (ng/dL) Following 
Administration of 237 mg TU BID with 30 g fat Breakfast 
(Treatment C) (PK Population) 
Table 14.2.1.1.9 
Plasma DHT Concentrations (ng/dL) Following 
Administration of 237 mg TU BID with 45 g fat Breakfast 
(Treatment D) (PK Population) 
Table 14.2.1.1.10 Plasma DHT Concentrations (ng/dL) Following 
Administration of 237 mg TU BID with FDA High-Calorie 
High-fat Breakfast (Treatment E) (PK Population) 
TU 
Table 14.2.1.1.11 Plasma TU Concentrations (ng/mL) Following 
Administration of 237 mg TU BID Under Fasting Condition 
for Breakfast (Treatment A) (PK Population) 
Table 14.2.1.1.12 Plasma TU Concentrations (ng/mL) Following 
Administration of 237 mg TU BID with 15 g fat Breakfast 
(Treatment B) (PK Population) 
Table 14.2.1.1.13 Plasma TU Concentrations (ng/mL) Following 
Administration of 237 mg TU BID with 30 g fat Breakfast 
(Treatment C) (PK Population) 
Table 14.2.1.1.14 Plasma TU Concentrations (ng/mL) Following 
Administration of 237 mg TU BID with 45 g fat Breakfast 
(Treatment D) (PK Population) 
Table 14.2.1.1.15 Plasma TU Concentrations (ng/mL) Following 
Administration of 237 mg TU BID with FDA High-Calorie 
High-fat Breakfast (Treatment E) (PK Population) 
 
 
 


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14.2.1.2 PK Parameter Tables 
 
Total T 
Table 14.2.1.2.1 
Plasma Total T Pharmacokinetic Parameters Following 
Administration of 237 mg TU BID Under Fasting Condition 
for Breakfast (Treatment A) (PK Evaluable Population) 
Table 14.2.1.2.2 
Plasma Total T Pharmacokinetic Parameters Following 
Administration of 237 mg TU BID with 15 g fat Breakfast 
(Treatment B) (PK Evaluable Population) 
Table 14.2.1.2.3 
Plasma Total T Pharmacokinetic Parameters Following 
Administration of 237 mg TU BID with 30 g fat Breakfast 
(Treatment C) (PK Evaluable Population) 
Table 14.2.1.2.4 
Plasma Total T Pharmacokinetic Parameters Following 
Administration of 237 mg TU BID with 45 g fat Breakfast 
(Treatment D) (PK Evaluable Population) 
Table 14.2.1.2.5 
Plasma Total T Pharmacokinetic Parameters Following 
Administration of 237 mg TU BID with FDA High-Calorie 
High-fat Breakfast (Treatment E) (PK Evaluable Population) 
DHT 
Table 14.2.1.2.6 
Plasma DHT Pharmacokinetic Parameters Following 
Administration of 237 mg TU BID Under Fasting Condition 
for Breakfast (Treatment A) (PK Evaluable Population) 
Table 14.2.1.2.7 
Plasma DHT Pharmacokinetic Parameters Following 
Administration of 237 mg TU BID with 15 g fat Breakfast 
(Treatment B) (PK Evaluable Population) 
Table 14.2.1.2.8 
Plasma DHT Pharmacokinetic Parameters Following 
Administration of 237 mg TU BID with 30 g fat Breakfast 
(Treatment C) (PK Evaluable Population) 
Table 14.2.1.2.9 
Plasma DHT Pharmacokinetic Parameters Following 
Administration of 237 mg TU BID with 45 g fat Breakfast 
(Treatment D) (PK Evaluable Population) 
Table 14.2.1.2.10 Plasma DHT Pharmacokinetic Parameters Following 
Administration of 237 mg TU BID with FDA High-Calorie 
High-fat Breakfast (Treatment E) (PK Evaluable Population) 
TU 
Table 14.2.1.2.11 Plasma TU Pharmacokinetic Parameters Following 
Administration of 237 mg TU BID Under Fasting Condition 
for Breakfast (Treatment A) (PK Evaluable Population) 
Table 14.2.1.2.12 Plasma TU Pharmacokinetic Parameters Following 
Administration of 237 mg TU BID with 15 g fat Breakfast 
(Treatment B) (PK Evaluable Population) 


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Table 14.2.1.2.13 Plasma TU Pharmacokinetic Parameters Following 
Administration of 237 mg TU BID with 30 g fat Breakfast 
(Treatment C) (PK Evaluable Population) 
Table 14.2.1.2.14 Plasma TU Pharmacokinetic Parameters Following 
Administration of 237 mg TU BID with 45 g fat Breakfast 
(Treatment D) (PK Evaluable Population) 
Table 14.2.1.2.15 Plasma TU Pharmacokinetic Parameters Following 
Administration of 237 mg TU BID with FDA High-Calorie 
High-fat Breakfast (Treatment E) (PK Evaluable Population) 
14.2.1.3 Statistical Analyses Tables 
 
Statistical Comparisons of Plasma Total T for Primary PK Parameters 
(Cmax-am, AUCam, Cavg-am) 
 
Primary Comparisons (Total T versus 30 g fat meal [C]): 
Table 14.2.1.3.1 
Primary Statistical Comparisons of Plasma Total T 
Pharmacokinetic Parameters: Treatment A (Test) Versus 
Treatment C (Reference) (PK Evaluable Population) 
Table 14.2.1.3.2 
Primary Statistical Comparisons of Plasma Total T 
Pharmacokinetic Parameters: Treatment B (Test) Versus 
Treatment C (Reference) (PK Evaluable Population) 
Table 14.2.1.3.3 
Primary Statistical Comparisons of Plasma Total T 
Pharmacokinetic Parameters: Treatment D (Test) Versus 
Treatment C (Reference) (PK Evaluable Population) 
Table 14.2.1.3.4 
Primary Statistical Comparisons of Plasma Total T 
Pharmacokinetic Parameters: Treatments E (Test) Versus 
Treatment C (Reference) (PK Evaluable Population) 
 


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Secondary Comparisons (Total T- versus 15 g fat meal [B]): 
Table 14.2.1.3.5 
Secondary Statistical Comparisons of Plasma Total T 
Pharmacokinetic Parameters: Treatment A (Test) Versus 
Treatment B (Reference) (PK Evaluable Population) 
Table 14.2.1.3.6 
Secondary Statistical Comparisons of Plasma Total T 
Pharmacokinetic Parameters: Treatment C (Test) Versus 
Treatment B (Reference) (PK Evaluable Population) 
Table 14.2.1.3.7 
Secondary Statistical Comparisons of Plasma Total T 
Pharmacokinetic Parameters: Treatment D (Test) Versus 
Treatment B (Reference) (PK Evaluable Population) 
Table 14.2.1.3.8 
Secondary Statistical Comparisons of Plasma Total T 
Pharmacokinetic Parameters: Treatment E (Test) Versus 
Treatment B (Reference) (PK Evaluable Population 
 
Secondary Comparisons (Total T – versus fasted state [A]): 
Table 14.2.1.3.9 
Secondary Statistical Comparisons of Plasma Total T 
Pharmacokinetic Parameters: Treatment B (Test) Versus 
Treatment A (Reference) (PK Evaluable Population) 
Table 14.2.1.3.10 Secondary Statistical Comparisons of Plasma Total T 
Pharmacokinetic Parameters: Treatment C (Test) Versus 
Treatment A (Reference) (PK Evaluable Population) 
Table 14.2.1.3.11 Secondary Statistical Comparisons of Plasma Total T 
Pharmacokinetic Parameters: Treatment D (Test) Versus 
Treatment A (Reference) (PK Evaluable Population) 
Table 14.2.1.3.12 Secondary Statistical Comparisons of Plasma Total T 
Pharmacokinetic Parameters: Treatment E (Test) Versus 
Treatment A (Reference) (PK Evaluable Population) 
 
Statistical Comparisons of Plasma Total T for Secondary PK Parameters 
(Cmax-pm, AUCpm, Cavg-pm, Cmax-24, and AUC24, Cavg-24) 
 
Secondary Comparisons (Total T – versus 30 g fat state[C]): 
Table 14.2.1.3.13 Secondary Statistical Comparisons of Plasma Total T 
Pharmacokinetic Parameters: Treatment A (Test) Versus 
Treatment C (Reference) (PK Evaluable Population) 
Table 14.2.1.3.14 Secondary Statistical Comparisons of Plasma Total T 
Pharmacokinetic Parameters: Treatment B (Test) Versus 
Treatment C (Reference) (PK Evaluable Population) 
Table 14.2.1.3.15 Secondary Statistical Comparisons of Plasma Total T 
Pharmacokinetic Parameters: Treatment D (Test) Versus 
Treatment C (Reference) (PK Evaluable Population) 


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Table 14.2.1.3.16 Secondary Statistical Comparisons of Plasma Total T 
Pharmacokinetic Parameters: Treatments E (Test) Versus 
Treatment C (Reference) (PK Evaluable Population) 
 
Secondary Comparisons (Total T – versus fasted state [A]): 
Table 14.2.1.3.17 Secondary Statistical Comparisons of Plasma Total T 
Pharmacokinetic Parameters: Treatment B (Test) Versus 
Treatment A (Reference) (PK Evaluable Population) 
Table 14.2.1.3.18 Secondary Statistical Comparisons of Plasma Total T 
Pharmacokinetic Parameters: Treatment C (Test) Versus 
Treatment A (Reference) (PK Evaluable Population) 
Table 14.2.1.3.19 Secondary Statistical Comparisons of Plasma Total T 
Pharmacokinetic Parameters: Treatment D (Test) Versus 
Treatment A (Reference) (PK Evaluable Population) 
Table 14.2.1.3.20 Secondary Statistical Comparisons of Plasma Total T 
Pharmacokinetic Parameters: Treatments E (Test) Versus 
Treatment A (Reference) (PK Evaluable Population) 
Statistical Comparisons of Plasma DHT for Secondary PK Parameters (Cmax-am, 
AUCam, Cmax-pm, AUCpm, Cmax-24, and AUC24): 
Secondary Comparisons (DHT): 
Table 14.2.1.3.21 Secondary Statistical Comparisons of Plasma DHT 
Pharmacokinetic Parameters: Treatment A (Test) Versus 
Treatment C (Reference) (PK Evaluable Population) 
Table 14.2.1.3.22 Secondary Statistical Comparisons of Plasma DHT 
Pharmacokinetic Parameters: Treatment B (Test) Versus 
Treatment C (Reference) (PK Evaluable Population) 
Table 14.2.1.3.23 Secondary Statistical Comparisons of Plasma DHT 
Pharmacokinetic Parameters: Treatment D (Test) Versus 
Treatment C (Reference) (PK Evaluable Population) 
Table 14.2.1.3.24 Secondary Statistical Comparisons of Plasma DHT 
Pharmacokinetic Parameters: Treatment E (Test) Versus 
Treatment C (Reference) (PK Evaluable Population) 
Statistical Comparisons of Plasma TU for Secondary PK Parameters (Cmax-am, 
AUCam, Cmax-pm, AUCpm, Cmax-24, and AUC24): 


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Secondary Comparisons (TU): 
Table 14.2.1.3.25 Secondary Statistical Comparisons of Plasma TU 
Pharmacokinetic Parameters: Treatment A (Test) Versus 
Treatment C (Reference) (PK Evaluable Population) 
Table 14.2.1.3.26 Secondary Statistical Comparisons of Plasma TU 
Pharmacokinetic Parameters: Treatment B (Test) Versus 
Treatment C (Reference) (PK Evaluable Population) 
Table 14.2.1.3.27 Secondary Statistical Comparisons of Plasma TU 
Pharmacokinetic Parameters: Treatment D (Test) Versus 
Treatment C (Reference) (PK Evaluable Population) 
Table 14.2.1.3.28 Secondary Statistical Comparisons of Plasma TU 
Pharmacokinetic Parameters: Treatment E (Test) Versus 
Treatment C (Reference) (PK Evaluable Population) 
 
Sensitivity Analysis: 
 
Primary Comparisons: 
Statistical Comparisons for Primary PK Parameters (Cmax-am, AUCam, 
Cavg-am): 
 
Table 14.2.1.4.1 
Statistical Comparisons of Plasma Total T Pharmacokinetic 
Parameters: Treatment A (Test) Versus Treatment C 
(Reference) (A Sub-Set of PK Evaluable Population) 
Table 14.2.1.4.2 
Statistical Comparisons of Plasma Total T Pharmacokinetic 
Parameters: Treatment B (Test) Versus Treatment C 
(Reference) (A Sub-Set of PK Evaluable Population) 
Table 14.2.1.4.3 
Statistical Comparisons of Plasma Total T Pharmacokinetic 
Parameters: Treatment D (Test) Versus Treatment C 
(Reference) (A Sub-Set of PK Evaluable Population) 
Table 14.2.1.4.4 
Statistical Comparisons of Plasma Total T Pharmacokinetic 
Parameters: Treatments E (Test) Versus Treatment C 
(Reference) (A Sub-Set of PK Evaluable Population) 
14.2.2. Figures 
14.2.2.1 Concentration Versus Time  
Figure 14.2.2.1.1 Mean (SD) Plasma Total T Concentrations Versus Time 
Following Treatments A, B, C, D, and E (Linear Scale) (PK 
Population) 
Figure 14.2.2.1.2 Mean Plasma Total T Concentrations Versus Time Following 
Treatments A, B, C, D, and E (Linear Scale) (PK Population) 


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Figure 14.2.2.1.3 Mean Plasma Total T Concentrations Versus Time Following 
Treatments A, B, C, D, and E (Semi-Log Scale) (PK 
Population) 
Figure 14.2.2.1.4 Mean (SD) Plasma DHT Concentrations Versus Time 
Following Treatments A, B, C, D, and E (Linear Scale) (PK 
Population) 
Figure 14.2.2.1.5 Mean Plasma DHT Concentrations Versus Time Following 
Treatments A, B, C, D, and E (Linear Scale) (PK Population) 
Figure 14.2.2.1.6 Mean Plasma DHT Concentrations Versus Time Following 
Treatments A, B, C, D, and E (Semi-Log Scale) (PK 
Population) 
Figure 14.2.2.1.7 Mean (SD) Plasma TU Concentrations Versus Time 
Following Treatments A, B, C, D, and E (Linear Scale) (PK 
Population) 
Figure 14.2.2.1.8 Mean Plasma TU Concentrations Versus Time Following 
Treatments A, B, C, D, and E (Linear Scale) (PK Population) 
Figure 14.2.2.1.9 Mean Plasma TU Concentrations Versus Time Following 
Treatments A, B, C, D, and E (Semi-Log Scale) (PK 
Population) 
 
Note: every figure will have 5 lines, 1 for each treatment. 
 
14.2.2.2 Food Effect  
 
Total T (Primary PK Parameters): 
Figure 14.2.2.2.1 
Effect of Food (Treatments A, B, C, D and E) on Plasma 
Total T Cmax-am (PK Evaluable Population) 
Figure 14.2.2.2.2 
Effect of Food (Treatments A, B, C, D and E) on Plasma 
Total T AUCam (PK Evaluable Population) 
Figure 14.2.2.2.3 
Effect of Food (Treatments A, B, C, D and E) on Plasma 
Total T Cavg-am (PK Evaluable Population) 
 
DHT (Secondary PK Parameters): 
Figure 14.2.2.2.4 
Effect of Food (Treatments A, B, C, D and E) on Plasma 
DHT Cmax-am (PK Evaluable Population) 
Figure 14.2.2.2.5 
Effect of Food (Treatments A, B, C, D and E) on Plasma 
DHT AUCam (PK Evaluable Population) 
 
TU (Secondary PK Parameters): 


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Figure 14.2.2.2.7 
Effect of Food (Treatments A, B, C, D and E) on Plasma 
TU Cmax-am (PK Evaluable Population) 
Figure 14.2.2.2.8 
Effect of Food (Treatments A, B, C, D and E) on Plasma 
TU AUCam (PK Evaluable Population) 
 
Note to programmer for Figures 14.2.2.2.1 through to 14.2.2.2.9: these are box 
plots of total T, DHT, and TU plasma Cmax0-12, and AUC0-12  (including 
individual values plotted, overlaid with the box plot) under each treatment 
(Treatments A, B, C, D, E) 
14.3 
Safety Data Summary Tables  
14.3.1 
Displays of Adverse Events 
Table 14.3.1.1 Treatment-Emergent Adverse Event Frequency by Phase – 
Number of Subjects Reporting Events (% of Subjects Dosed) 
Table 14.3.1.2 Treatment-Emergent Adverse Event Frequency by Phase – 
Number of Adverse Events (% of Total Adverse Events) 
Table 14.3.1.3 Treatment-Emergent Adverse Event Frequency by Severity 
and Relationship to Drug – Number of Subjects Reporting 
Events 
Table 14.3.1.4 Treatment-Emergent Adverse Event Frequency by Severity 
and Relationship to Drug – Number of Adverse Events 
14.3.2 
Listings of Deaths, other Serious and Significant Adverse Events 
Table 14.3.2.1 Serious Adverse Events  
If no serious adverse event occurred, a statement ‘No serious 
adverse event was reported’ 
Table 14.3.2.2 Serious Adverse Events Resulting in Discontinuation From 
Study Drug 
If no serious adverse event resulting in discontinuation from 
study drug occurred, a statement ‘No serious adverse event 
resulting in discontinuation was reported’ 
Table 14.3.2.3 Serious Adverse Events Resulting in Death 
If no serious adverse event resulting in death occurred, a 
statement ‘No serious adverse event resulting in death was 
reported’ 
14.3.3. Narratives of Deaths, other Serious and Certain other 
Significant Adverse Events 
Not programmed – included as text in the report 
14.3.4. Abnormal Laboratory Value Listing (each subject) 
Table 14.3.4.1 Out-of-Range Values and Recheck Results –Chemistry 


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Table 14.3.4.2 Out-of-Range Values and Recheck Results – Hematology 
Table 14.3.4.3 Out-of-Range Values and Recheck Results – Urinalysis 
14.3.5. Displays of Other Laboratory, Vital Signs, Physical 
Examination, and Other Safety Data 
Table 14.3.5.1 Clinical Laboratory Summary and Change From Baseline –
Chemistry 
Table 14.3.5.2 Clinical Laboratory Summary and Change From Baseline – 
Hematology 
Table 14.3.5.3 Clinical Laboratory Summary – Urinalysis 
Table 14.3.5.4 Vital Sign Summary  
Table 14.3.5.5 Vital Sign Change From Baseline 
8.3 
Section 16 Data Listings 
Data listings are numbered following the ICH structure but may be renumbered as 
appropriate during the compilation of the tables and figures for the report. The 
following is a list of appendix numbers and titles that will be included as data listings: 
16.1. Study Information 
Appendix 16.1.10.1 
Clinical Laboratory Reference Ranges 
16.2. Subject Data Listings 
16.2.1. Subject Discontinuation 
Appendix 16.2.1 Subject Disposition 
16.2.2. Protocol Deviations 
Appendix 16.2.2 Protocol Deviations 
16.2.3. Subjects Excluded from Pharmacokinetic Analysis 
Appendix 16.2.3 Subjects Excluded from Pharmacokinetic Analysis (PK 
Population) 
 
Note:  Appendices 16.2.2 and 16.2.3 are generated in MS Word for inclusion 
in the study report. 
16.2.4. Demographic Data 
Appendix 16.2.4.1 
Demographics 
Appendix 16.2.4.2.1 Physical Examination (I of II) 
Appendix 16.2.4.2.2 Physical Examination (II of II) 


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Appendix 16.2.4.2.3 Physical Examination Descriptions 
Appendix 16.2.4.3 
Medical and Surgical History 
Appendix 16.2.4.4 
Testosterone Replacement Therapy – Screening 
Appendix 16.2.4.5 
Hypogonadism Signs and Symptoms – Screening 
Appendix 16.2.4.6 
International Prostate Symptom Score (I-PSS) and 
Quality of Life Due to Urinary Symptoms Score -
Screening 
16.2.5. Compliance and Drug Concentration Data 
Appendix 16.2.5.2 
Subject Eligibility  
Appendix 16.2.5.3 
Dosing – Run-In Phase Days 1and 14 
Appendix 16.2.5.4 
Dose Accountability – Run-In Phase, Days 1-14 
Appendix 16.2.5.5 
Dosing – PK Phase  
Appendix 16.2.5.6 
Blood Draw Times 
Appendix 16.2.5.7 
Meal Times 
Appendix 16.2.5.8.1 Prior Medications 
Appendix 16.2.5.8.2 Concomitant Medications 
16.2.6. Individual Pharmacokinetic Response Data 
Appendix 16.2.6.1.1-16.2.6.1.X Individual Plasma Total T Concentrations 
Versus Time (Linear and Semi-Log Scale) Following 
Treatments A, B, C, D, and E (PK Population) 
Appendix 16.2.6.2.1-16.2.6.2.X Individual Plasma DHT Concentrations 
Versus Time (Linear and Semi-Log Scale) Following 
Treatments A, B, C, D, and E (PK Population) 
Appendix 16.2.6.3.1 16.2.6.3.X Individual Plasma TU Concentrations 
Versus Time (Linear and Semi-Log Scale) Following 
Treatments A, B, C, D, and E (PK Population) 
 
Note to programmer: Figures 16.2.6.1-16.2.6.3 are by subject; therefore the 
number of plots equals the number of subjects for each Appendix. 
 
16.2.7. Individual Adverse Event Listings 
Appendix 16.2.7.1 
Adverse Events (I of II) 
Appendix 16.2.7.2 
Adverse Events (II of II) 
16.2.8. Individual Laboratory Measurements 
Appendix 16.2.8.1 
Clinical Laboratory Report - Chemistry 


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Appendix 16.2.8.2 
Clinical Laboratory Report - Hematology  
Appendix 16.2.8.3 
Clinical Laboratory Report - Urinalysis  
Appendix 16.2.8.4 
Clinical Laboratory Report – Other 
Appendix 16.2.8.5 
Clinical Laboratory Report - Comments 
Appendix 16.2.8.6 
Vital Signs 
Appendix 16.2.8.7 
Vital Signs – Average of Triplicate Values 
Appendix 16.2.8.8 
Phone Call – Safety Follow-Up Phase 
Appendix 16.2.8.9 
Study Completion/Early Termination 
Appendix 16.2.8.10  General Comments 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 34 of 87 
9. TABLE SHELLS  
The following table shells provide a framework for the display of data from this 
study. The shells may change due to unforeseen circumstances. These shells may not 
be reflective of every aspect of this study, but are intended to show the general layout 
of the tables that will be presented and included in the final report. 
 
 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 35 of 87 
Table 10-1 
Disposition Summary 
 
Disposition 
Overall 
Enrolled and Randomized 
X (XX%) 
Dosed 
  X (XX%) 
Completed 
 X (XX%) 
Discontinued 
  X (X%)     
 
<Reason1> 
  X (X%)     
 
<Reason2> 
  X (X%)     
Source: Table 14.1.1 
Program:  /CAXXXXX/sas_prg/stsas/intexttest/t_disp.sas  DDMMMYYYY  
HH:MM 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 36 of 87 
Table 10-2 
Demographic Summary 
 
Trait 
Category/Statistics 
Overall 
Gender 
Male 
  X (XXX%) 
Race 
Asian 
  X (XX%)   
 
Black or African American 
  X (XX%)   
 
White 
  X (XX%)   
Ethnicity 
Hispanic or Latino 
  X (XXX%) 
 
Not Hispanic or Latino 
  X (XXX%) 
Age (yrs) 
n 
 X 
 
Mean 
 XX.X 
 
SD 
 XX.XX 
 
Minimum 
 XX 
 
Median 
 XX.X 
 
Maximum 
 XX 
Weight (kg) 
n 
 X 
 
Mean 
 XX.XX 
 
SD 
 XX.XXX 
 
Minimum 
 XX.X 
 
Median 
 XX.XX 
 
Maximum 
 XX.X 
Height (cm) 
n 
 X 
 
Mean 
 XXX.X 
 
SD 
 XX.XX 
 
Minimum 
 XXX 
 
Median 
 XXX.X 
 
Maximum 
 XXX 
PSA (units) 
n 
 X 
 
Mean 
 XXX.X 
 
SD 
 XX.XX 
 
Minimum 
 XXX 
 
Median 
 XXX.X 
 
Maximum 
 XXX 
BMI (kg/m²) 
n 
 X 
 
Mean 
 XX.XXX 
 
SD 
 X.XXXX 
 
Minimum 
 XX.XX 
 
Median 
 XX.XXX 
 
Maximum 
 XX.XX 
I-PSS 
n 
 X 
 
Mean 
 XX.XXX 
 
SD 
 X.XXXX 
 
Minimum 
 XX.XX 
 
Median 
 XX.XXX 
 
Maximum 
 XX.XX 
I-PSS QOL  
n 
 X 
 
Mean 
 XX.XXX 
 
SD 
 X.XXXX 
 
Minimum 
 XX.XX 
 
Median 
 XX.XXX 
 
Maximum 
 XX.XX 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 37 of 87 
Trait 
Category/Statistics 
Overall 
BMI = Body mass index 
PSA = Prostate specific antigen 
I-PSS = International Prostate Symptom Score (Questions 1-7) 
QOL = Quality of Life Due to Urinary Symptoms Score (Question 8 in I-PSS) 
Age is calculated at the time of informed consent 
Source: Table 14.1.3 
Program:  /CAXXXXX/sas_prg/stsas/intexttest/t_dem.sas  DDMMMYYYY  HH:MM 
 
 
 
 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 38 of 87 
Tables 11-1, 11-7, and 11-9 will be in the following format: 
Table 11-X 
Summary of Plasma Total T Pharmacokinetic Parameters Following Treatments A, B, C, D, 
and E (PK Evaluable Population) 
 
 
Treatment X 
Treatment X 
Pharmacokinetic Parameters 
GM (GCV%) 
n 
GM (GCV%) 
n 
Post-AM Dose 
Param1 (units)   
XXX.X (XX.X) 
XX 
XXX.X (XX.X) 
XX 
Param2 (units)   
XXX.X (XX.X) 
XX 
XXX.X (XX.X) 
XX 
Param3 (units)   
XXX.X (XX.X) 
XX 
XXX.X (XX.X) 
XX 
Param4 (units)   
XXX.X (XX.X) 
XX 
XXX.X (XX.X) 
XX 
Treatment A: 237 mg TU Administered BID Under Fasting Condition for Breakfast 
Treatment B: 237 mg TU Administered BID with 15 g fat for Breakfast 
Treatment C: 237 mg TU Administered BID with 30 g fat for Breakfast 
Treatment D: 237 mg TU Administered BID with 45 g fat for Breakfast 
Treatment E: 237 mg TU Administered BID with FDA High-Calorie, High-fat for Breakfast 
n = Number of observations used in the analysis. 
Tmax0-12 and Tmax12-24 are presented as Median (Minimum, Maximum). 
AUC, Cmax and Cavg are presented as Geometric Mean (GM) and Geometric Coefficient of Variation % (GCV%) 
Source: Tables 14.2.1.2.1 through to 14.2.1.2.5, (Table 11-1)Tables 14.2.1.2.6 through to 14.2.1.2.10 (Table 11-7), and 
Tables 14.2.1.2.11 through to 14.2.1.2.15 (Table 11-9) 
Program:  /CAXXXXX/sas_prg/pksas/programname.sas  DDMMMYYYY  HH:MM 
 
Notes for Generating the Actual Table: 
 
Presentation of Data: 
Note: ask PKist which subjects to exclude (subjects that did not eat all the fat-containing items 
of their meal are not part of the PK Evaluable Population) 
 
The following PK parameters will be presented in Table 11-1,11-5, and 11-6: AUCam (unit), 
AUCpm (unit), AUC24 (unit), Cmax-am (unit), Cmax-pm (unit), Cmax-24 (unit), Tmax-am (hr), 
Tmax-pm (hr), Cavg-am (unit), Cavg-pm(unit), and Cavg-24 (unit).  
 
There will be two columns (GM (GVC%) and n) per Treatment (only 2 in example above; 
however, there are 5 treatments). The five treatments are as follows: 
Treatment A: 237 mg TU Administered BID Under Fasting Condition for Breakfast 
Treatment B: 237 mg TU Administered BID with 15 g fat Breakfast 
Treatment C: 237 mg TU Administered BID with 30 g fat Breakfast 
Treatment D: 237 mg TU Administered BID with 45 g fat Breakfast 
Treatment E: 237 mg TU Administered BID with FDA High-Calorie, High-fat Breakfast 
 
n will be presented as an integer (with no decimal). 
 
Summary statistics will be presented with same precision as defined in post-text shells  
 
Please use Table ITPar1 internal template.    
 
Program:  /CAXXXXX/sas_prg/pksas/adam_intext_pkparam.sas DDMMMYYYY  HH:MM 
 
 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 39 of 87 
Tables 11-2 through 11-6 and Tables 11-8, and11-10 will be in the following format: 
Table 11-X Statistical Comparisons of Plasma Total T Pharmacokinetic Parameters: 
Treatments <>, <> <> and <> Versus Treatment <> (Reference) (PK Evaluable Population) 
Pharmacokinetic 
 Parameters 
Treatment A 
Treatment B 
Treatment C 
Treatment D 
Treatment E 
Intra-
Subject 
CV% 
n 
Geometric 
LSMs 
n 
Geometric 
LSMs 
n 
Geometric 
LSMs 
 n  
Geometric 
LSMs 
 n  
Geometric 
LSMs 
Param 1 (units) 
XX 
XXX.X 
XX 
XXX.X 
XX 
XXX.X 
XX 
XXX.X 
XX 
XXX.X 
X.XX 
Param 2 (units) 
XX 
XXX.X 
XX 
XXX.X 
XX 
XXX.X 
XX 
XXX.X 
XX 
XXX.X 
X.XX 
Param 3 (units) 
XX 
XXX.X 
XX 
XXX.X 
XX 
XXX.X 
XX 
XXX.X 
XX 
XXX.X 
X.XX 
Pharmacokinetic 
 Parameters 
Treatment 
<>/Treatment <> 
Treatment 
<>/Treatment <> 
Treatment <>/Treatment 
<> 
Treatment <>/Treatment 
<> 
GMR 
90% CI 
GMR 
90% CI 
GMR 
90% CI 
GMR 
90% CI 
Param 1 (units) 
X.XX 
X.XX, X.XX 
X.XX 
X.XX, X.XX 
X.XX 
X.XX, X.XX 
X.XX 
X.XX, X.XX 
Param 2 (units) 
X.XX 
X.XX, X.XX 
X.XX 
X.XX, X.XX 
X.XX 
X.XX, X.XX 
X.XX 
X.XX, X.XX 
Param 3 (units) 
X.XX 
X.XX, X.XX 
X.XX 
X.XX, X.XX 
X.XX 
X.XX, X.XX 
X.XX 
X.XX, X.XX 
Treatment A: 237 mg TU Administered BID Under Fasting Condition for Breakfast 
Treatment B: 237 mg TU Administered BID with 15 g fat Breakfast 
Treatment C: 237 mg TU Administered BID with 30 g fat Breakfast 
Treatment D: 237 mg TU Administered BID with 45 g fat Breakfast 
Treatment E: 237 mg TU Administered BID with FDA High-Calorie, High-fat Breakfast 
 
Geometric least-squares means (LSMs) are calculated by exponentiating the LSMs derived from the linear mixed-effects model. 
Geometric mean ratio (GMR) = 100 x (test/reference) 
Intra-subject CV% was calculated as 100 x square root (exp[residual variance]-1). 
n = Number of observations used in the analysis.1 
Notes for Generating the Actual Table: 
 
Presentation of Data: 
Note: ask PKist which subjects to exclude (subjects that did not eat all the fat-containing items 
of their meal are not part of the PK Evaluable Population) 
 
The following PK parameters will be presented in Tables 11-2, 11-3, and 11-4: (Cmax-am, 
AUCam, and Cavg-am). 
 
The following PK parameters will be presented in Tables 11-7, 11-8, and 11-9: (Cmax-pm, 
AUCpm, Cavg-pm, Cmax24, AUC24, and Cavg-24) 
 
n will be presented as an integer (with no decimal); 
 
All statistics will be presented with same precision as defined in post-text shells 
 
Treatments for each table, and source tables are the following: 
o 
Table 11-2: source table 14.2.1.3.1-4 
o 
Table 11-3: source table 14.2.1.3.5-8 
o 
Table 11-4: source table 14.2.1.3.9-12 
o 
Table 11-5: source table 14.2.1.3.13-16 
o 
Table 11-6: source table 14.2.1.3.17-20 
o 
Table 11-8: source table 14.2.1.3.21-24 
o 
Table 11-10: source table 14.2.1.3.25-8 
o 
Table 11-11: source table 14.2.1.4.1-4 
 
Please add the respective treatment descriptions for each table, as relevant, from the 
following:  
Treatment A: 237 mg TU Administered BID Under Fasting Condition for Breakfast 
Treatment B: 237 mg TU Administered BID with 15 g fat Breakfast 
Treatment C: 237 mg TU Administered BID with 30 g fat Breakfast 
Treatment D: 237 mg TU Administered BID with 45 g fat Breakfast 
Treatment E: 237 mg TU Administered BID with FDA High-Calorie, High-fat Breakfast 
Programmer’s note: 
 
Please use Table ITPStat1 internal template.    
 
No changes are made to this table relative to Celerion standard. 
 
Program:  /CAXXXXX/sas_prg/pksas/adam_intext_pkparam.sas DDMMMYYYY  HH:MM 
 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 40 of 87 
Table 12-1 
Incidence of Treatment-Emergent Adverse Events by Phase 
 
Adverse Events* 
Run-In and PK Phase 
 
Follow-Up Phase 
Overall 
Number of Subjects Enrolled and Randomized 
X (100%) 
X (100%) 
X (100%) 
Number of Subjects Dosed 
X (100%) 
X (100%) 
X (100%) 
Number of Subjects With Adverse Events 
X (XX%) 
X (XX%) 
X (XX%) 
Number of Subjects Without Adverse Events 
X (XX%) 
X (XX%) 
X (XX%) 
General disorders and administration site conditions 
X (XX%) 
X (XX%) 
X (XX%) 
     Vessel puncture site pain 
X (XX%) 
X (XX%) 
X (XX%) 
     Vessel puncture site reaction 
X (XX%) 
X (XX%) 
X (XX%) 
*Adverse events are classified according to MedDRA® Version 15.1 
Although a subject may have had 2 or more clinical adverse experiences, the subject is counted only once within a category. The same 
subject may appear in different categories. 
Source: Table 14.3.1.1 
Program:  /CAXXXXX/sas_prg/stsas/intexttest/t_ae.sas  DDMMMYYYY  HH:MM 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 41 of 87 
Post-text TFLs will be as follows: 
 
Part 1 of X 
 
Table 14.1.1  Summary of Disposition 
 
                                      Disposition                      Overall    
                                      ------------------------------------------- 
                                      Enrolled and Randomized         XX (XX.X%)  
                                      Dosed                           XX ( 100%)  
                                      Completed Study                 XX (XX.X%)  
                                      Discontinued Early              XX (XX.X%)  
                                        <Reason>                      XX (XX.X%)  
 
 
 
 
 
 
 
 
 
 
Program:  /CAXXXXX/sas_prg/stsas/tab_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 42 of 87 
Page 1 of X 
 
Table 14.1.2  Disposition of Subjects 
 
                   Dosed For PK Phase Period                        Study Completion              
          Subject  -----------------------             ---------------------------------------    
          Number   1     2    3    4    5              Status                         Date        
          -------------------------------------------------------------------------------------   
              X    Yes  No   No   No   No              Terminated Study Prematurely  DDMMMYYYY    
              X    Yes  Yes  Yes  Yes  Yes             Completed Study               DDMMNYYYY    
              X    Yes  Yes  Yes  Yes  Yes             Completed Study               DDMMMYYYY    
              X    Yes  Yes  Yes  Yes  Yes             Completed Study               DDMMMYYYY    
              X    Yes  Yes  Yes  Yes  Yes             Completed Study               DDMMMYYYY    
              X    Yes  Yes  Yes  Yes  Yes             Completed Study               DDMMMYYYY    
              X    Yes  Yes  Yes  Yes  Yes             Completed Study               DDMMMYYYY    
              X    Yes  Yes  Yes  Yes  Yes             Completed Study               DDMMMYYYY    
              X    Yes  Yes  Yes  Yes  Yes             Completed Study               DDMMMYYYY    
              X    Yes  Yes  Yes  Yes  Yes             Completed Study               DDMMMYYYY    
                   ---  ---  ---  ---  ---                                                        
                   XX   XX   XX   XX   XX                                                         
 
 
 
 
 
 
 
 
 
Program:  /CAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 43 of 87 
Page 1 of X 
 
Table 14.1.3  Demographic Summary 
 
                           Trait                                    Overall     
                           ---------------------------------------------------- 
                           Gender          Male                     X (XX.X%)   
                                                                                
                           Race            XXXXXXXXXXXXXXX          X (XX.X%)   
                                                                                
                           Ethnicity       XXXXXXXXXXXXXXX          X (XX.X%)   
 
                           Age* (yrs)      n                               X    
                                           Mean                          X.X    
                                           SD                           X.XX    
                                           Minimum                        XX    
                                           Median                        X.X    
                                           Maximum                        XX    
                                                                                 
                           Weight (kg)     n                               X    
                                           Mean                          X.X    
                                           SD                           X.XX    
                                           Minimum                        XX    
                                           Median                        X.X    
                                           Maximum                        XX    
 
 
<Continued with other measures – height, BMI, PSA, I-PSS, I-PSS-QOL> 
 
 
 
Note:  * Age is calculated from informed consent date. 
 
Program:  /CAXXXXX/sas_prg/stsas/tab_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 
 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 44 of 87 
Tables 14.2.1.1.1-15 will be formatted as:   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page X of X 
Table 14.2.1.1.X  
Plasma Total <> Concentrations (unit) Following <> Treatment <> (PK Population) 
 
Subject 
Treatment 
Study 
--------------------- Sample Times (hr) ------------------------ 
 
Number 
Sequence Period Predose 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXX-XXX 
XXX 
X 
BLQ 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XXX-XXX 
XXX 
X 
BLQ 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XXX-XXX 
XXX 
X 
BLQ 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
n 
 
 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
 
 
XX.X 
XX.X 
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 
XX.XX 
XX.XX 
CV% 
 
 
. 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
SEM 
 
 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Minimum 
 
 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
 
 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
Maximum 
 
 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
For the calculation of summary statistics, values that are below the limit of quantitation (BLQ) of <XX> are treated as <0>  
before the first quantifiable concentration and as missing elsewhere. 
. = Value missing or not reportable.  
 
 
Notes for Generating the Actual Table: 
 
Presentation of Data: 
 
Concentrations will be presented to same precision as in bio data.  
 
Summary statistics presentation with respect to the precision of the bio data: n = integer; Mean, Median+1; SD and SEM +2, Min and 
Max +0, and CV% to 1 decimal 
 
Tables 14.2.1.1.1 to 14.2.1.1.5 will present Total T concentrations (ng/dL); Tables 14.2.1.1.6 to 14.2.1.1.10 will present DHT 
concentrations (ng/dL) and Tables 14.2.1.1.11 to 14.2.1.1.15 will present TU concentration (ng/mL). 
 
Programmer Note:  


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 45 of 87 
 
PK Time points are 0 (predose), 2, 4, 6, 9, 12, 14, 16, 18, 21 and 24 hours post-AM dose. 24 hour time points for PK Period 1, 2,3 
and 4 are the same as 0 for PK Period 2,3, 4 and 5. 
 
Please add the following footnote since sequence will contain these abbreviations:  
 
 
Treatment A: 237 mg TU Administered BID Under Fasting Condition for Breakfast 
Treatment B: 237 mg TU Administered BID with 15 g fat Breakfast 
Treatment C: 237 mg TU Administered BID with 30 g fat Breakfast 
Treatment D: 237 mg TU Administered BID with 45 g fat Breakfast 
Treatment E: 237 mg TU Administered BID with FDA High-Calorie, High-fat Breakfast 
 
Program:  /CAXXXXX/sas_prg/pksas/pk-conc-tables.sas   
 
DDMMMYYYY  HH:MM 
Program:  /CAXXXXX/sas_prg/pksas/pk-conc-tables-sig.sas   DDMMMYYYY  HH:MM 
 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 46 of 87 
Tables 14.2.1.2.1 through to 14.2.1.2.15 will be formatted as: 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page X of X   
Table 14.2.1.2.X Plasma Total T Pharmacokinetic Parameters Following <> Treatment <> (PK Evaluable 
Population) 
                                                      ------------------------------------ Parameters ----------------------------- 
Subject 
Treatment 
Study 
param1 
param2 
param3 
param4 
param5 
param6 
Number 
Sequence 
Period 
(units) 
(units) 
(units) 
(units) 
(units) 
(units) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXX-XXX 
XXX 
X 
XXX 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
XXX-XXX 
XXX 
X 
XX.X 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
XXX-XXX 
XXX 
X 
XXX 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
XXX-XXX 
XXX 
X 
XX.X 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
XXX-XXX 
XXX 
X 
XX.X 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
XXX-XXX 
XXX 
X 
X.XX 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
XXX-XXX 
XXX 
X 
XXX 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
n 
 
 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
 
 
XXX.X 
X.XXX 
XXX.X 
XXX.X 
XX.XX 
X.XXXX 
SD 
 
 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
CV% 
 
 
. 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
SEM 
 
 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Minimum 
 
 
XX.X 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
Median 
 
 
XX.XX 
X.XXX 
XXX.X 
XXX.X 
XX.XX 
X.XXXX 
Maximum 
 
 
XXX 
X.XX 
XXX 
XXX 
XX.X 
X.XXX 
Geom Mean 
 
 
XXX.X 
X.XXX 
XXX.X 
XXX.X 
XX.XX 
X.XXXX 
Geom CV% 
 
 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
    -------------------------------------------------------------------------------------------------------------------------------- 
         . = Value missing or not reportable. 
 
 
 
Notes for Generating the Actual Table: 
 
Presentation of Data: 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 47 of 87 
Note: ask PKist which subjects to exclude (subjects that did not eat all the fat-containing items of their meal are not part of the PK 
Evaluable Population) 
 
PK Parameters will be presented in the following order: AUC0-12 (unit), AUC12-24 (unit), AUC24 (unit), Cmax0-12 (unit), Cmax12-24 
(unit), Cmax24 (unit), Tmax0-12 (hr), Tmax12-24 (hr), Cavg0-12 (unit), Cavg12-24(unit), and Cavg0-24 (unit)..  
 
Please add the following footer:  
Treatment A: 237 mg TU Administered BID under Fasting Condition for Breakfast 
Treatment B: 237 mg TU administered BID with 15 g fat Breakfast 
Treatment C: 237 mg TU Administered BID with 30 g fat Breakfast 
Treatment D: 237 mg TU Administered BID with 45 g fat Breakfast 
Treatment E: 237 mg TU Administered BID with FDA High-Calorie, High-fat Breakfast 
 
n will be presented as an integer (with no decimal); 
 
Parameter values for exposure based parameters (i.e. AUCs, Cmax, Cavg) will be presented with 3 significant figures.  
 
Summary statistics for exposure parameters will be presented as: Mean, Median, Geom Mean +1; SD and SEM +2, Min and Max +0.  
 
Values for Tmax and its summary statistics of Mean, SD, SEM, Minimum, Median, Maximum and Geom Mean, will be presented  
 
CV% and Geom CV% for all parameters will be presented with 1 decimal 
 
Program:  /CAXXXXX/sas_prg/pksas/pk-tables.sas   
DDMMMYYYY  HH:MM 
Program:  /CAXXXXX/sas_prg/pksas/adam_pkparam.sas   DDMMMYYYY  HH:MM 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 48 of 87 
Tables 14.2.1.3.1 through to 14.2.1.3.28 and Tables 14.2.1.4.1-4 will have the following format: 
                                                                                                                               Page X of X 
Table 14.2.1.3.X Statistical Comparisons of Plasma Total T Pharmacokinetic Parameters: Treatment <> (Test) 
Versus Treatment <> (Reference) Conditions (PK Evaluable Population) 
 
 
 
Treatment 
----- Geometric LSMs ----- 
 
Geometric 
 
 
 
 
 
 
 
 
Mean 
Confidence Intervals 
Intra-subject 
Parameter 
(unit) 
<> 
(n) 
<> 
(n) 
Ratio 
(90% Confidence) 
CV% 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Param1 
(unit) 
X.XX 
(n) 
X.XX 
(n) 
X.XX 
XX.XX - XXX.XX 
X.XX 
Param2 
(unit) 
X.XX 
(n) 
X.XX 
(n) 
X.XX 
XX.XX - XXX.XX 
X.XX 
Param3 
(unit) 
X.XX 
(n) 
X.XX 
(n) 
X.XX 
XX.XX - XXX.XX 
X.XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment A: 237 mg TU Administered BID Under Fasting Condition for Breakfast 
Treatment B: 237 mg TU Administered BID with 15 g fat Breakfast 
Treatment C: 237 mg TU Administered BID with 30 g fat Breakfast 
Treatment D: 237 mg TU Administered BID with 45 g fat Breakfast 
Treatment E: 237 mg TU Administered BID with FDA High-Calorie, High-fat Breakfast 
 
Parameters were ln-transformed prior to analysis.  
Geometric least-squares means (LSMs) are calculated by exponentiating the LSMs from the linear mixed-effects model. 
Geometric Mean Ratio = exp(test-reference) 
Intra-subject CV (%CV) = 100 x square root(exp[MSE]-1)] 
MSE = Residual variance from the linear mixed-effects model. 
n = Number of observations used in the analysis. 
Notes for Generating the Actual Table: 
 
Presentation of Data: 
 
PK Parameters are: 
Tables 14.2.1.3.1-12: Cmax-am, AUCam, Cavg-am 
Tables 14.2.1.3.13-20: Cmax-pm, AUCpm, Cavg-pm, Cmax-24, and AUC24, Cavg-24 
Tables 14.2.1.3.21-24: Cmax-am, AUCam, Cmax-pm, AUCpm, Cmax-24, and AUC24 


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Statistical Analysis Plan 
23 March 2017 
 
Page 49 of 87 
Tables 14.2.1.3.25-28:  Cmax-am, AUCam, Cmax-pm, AUCpm, Cmax-24, and AUC24 
Tables 14.2.1.4.1-4: Cmax-am, AUCam, Cavg-am 
• 
Geometric LSMs be presented to same precision as Mean in the PK parameter table CPPar1, 
• 
Geometric Mean Ratio, 90% CI and intra-subject CV% will be presented to 2 decimal places. 
Program:  /CAXXXXX/sas_prg/pksas/stats-tables-mixed.sas   DDMMMYYYY  HH:MM  
 


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Statistical Analysis Plan 
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Page 50 of 87 
age 1 of 1 
Table 14.3.1.1 Treatment-Emergent Adverse Event Frequency by Phase - Number of Subjects Reporting Events (% of Subjects Dosed) 
 
 
                                                                              Run-In and  Follow-Up 
                        Adverse Event*                                        PK Phase    Phase         Total   
                        --------------------------------------------------------------------------------------   
                        Number Enrolled/ Randomized 
                        Number of Subjects Dosed                             XX (XXX%)    XX (XXX%)  XX (XXX%)   
                        Number of Subjects With TE Adverse Events             X ( XX%)     X ( XX%)   X ( XX%)   
                        Number of Subjects Without TE Adverse Events         XX ( XX%)    XX ( XX%)  XX ( XX%)   
                        ---------------------------------------------------------------------------------------  
                        Nervous system disorders                              X (  X%)     X (  X%)   X (  X%)   
                             Dizziness                                        X (  X%)     X (  X%)   X (  X%)   
                             Headache                                         X (  X%)     X (  X%)   X (  X%)   
                             Presyncope                                       X (  X%)     X (  X%)   X (  X%)   
                        Respiratory, thoracic and mediastinal disorders       X (  X%)     X (  X%)   X (  X%)   
                             Dry throat                                       X (  X%)     X (  X%)   X (  X%)   
                             Oropharyngeal pain                               X (  X%)     X (  X%)   X (  X%)   
                             Sinus congestion                                 X (  X%)     X (  X%)   X (  X%)   
                             Sneezing                                         X (  X%)     X (  X%)   X (  X%)   
                        General disorders and administration site             X (  X%)     X (  X%)   X (  X%)   
                        conditions 
                             Fatigue                                          X (  X%)     X (  X%)   X (  X%)   
                             Thirst                                           X (  X%)     X (  X%)   X (  X%)   
       
Note:  * Adverse events are classified according to MedDRA Version 15.1. 
 
Program:  /CAXXXXX/sas_prg/stsas/tab_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 
 
 
 
 


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Statistical Analysis Plan 
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Page 51 of 87 
Page 1 of 1 
 
Table 14.3.1.2  Treatment-Emergent Adverse Event Frequency by Phase - Number of Adverse Events (% of Total Adverse Events) 
 
 
                                                                              Run-In and   Follow-Up 
                        Adverse Event*                                        PK Phase     Phase         Total    
                        ---------------------------------------------------------------------------------------   
                        Number of Adverse Events                              X (XXX%)      X (XXX%)   X (XXX%)  
                        ----------------------------------------------------------------------------------------- 
                        Nervous system disorders                              X (  X%)      X (  X%)   X (  X%)   
                             Dizziness                                        X (  X%)      X (  X%)   X (  X%)   
                             Headache                                         X (  X%)      X (  X%)   X (  X%)   
                             Presyncope                                       X (  X%)      X (  X%)   X (  X%)   
                        Respiratory, thoracic and mediastinal disorders       X (  X%)      X (  X%)   X (  X%)   
                             Dry throat                                       X (  X%)      X (  X%)   X (  X%)   
                             Oropharyngeal pain                               X (  X%)      X (  X%)   X (  X%)   
                             Sinus congestion                                 X (  X%)      X (  X%)   X (  X%)   
                             Sneezing                                         X (  X%)      X (  X%)   X (  X%)   
                        General disorders and administration site             X (  X%)      X (  X%)   X (  X%)   
                        conditions  
                             Fatigue                                          X (  X%)      X (  X%)   X (  X%)   
                             Thirst                                           X (  X%)      X (  X%)   X (  X%)   
        
Note:  * Adverse events are classified according to MedDRA Version 15.1. 
 
 
 
 
Program:  /CAXXXXX/sas_prg/stsas/tab_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 
 
 


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Statistical Analysis Plan 
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Page 1 of 1 
 
Table 14.3.1.3  Treatment-Emergent Adverse Event Frequency by Severity and Relationship to Drug 
Number of Subjects Reporting Events  
 
                                                                                           Relationship to Study Drug 
                                                                                 --------------------------- --------------------- 
                                       Number of         Severity/Intensity      Definitely Probably 
                                      Subjects with    ----------------------    Not        Not      Possibly  Probably 
   Adverse Event*    Phase            Adverse Events   Mild  Moderate  Severe    Related    Related  Related   Related  Definitely 
   ------------------------------------------------------------------------------------------------------------------------------- 
   Dizziness         Run-In and PK          X           X       X         X         X         X         X         X         X      
                     Follow-Up              X           X       X         X         X         X         X         X         X      
   Dry eye           Follow-Up              X           X       X         X         X         X         X         X         X      
   Dry mouth         XXXXXXXXXXXXX          X           X       X         X         X         X         X         X         X      
   Ear pain          XXXXXXXXXXXXX          X           X       X         X         X         X         X         X         X      
                     XXXXXXXXXXXXX          X           X       X         X         X         X         X         X         X      
   Fatigue           XXXXXXXXXXXXX          X           X       X         X         X         X         X         X         X      
   Headache          XXXXXXXXXXXXX          X           X       X         X         X         X         X         X         X      
   Hyperhidrosis     XXXXXXXXXXXXX          X           X       X         X         X         X         X         X         X      
 
   ------------------------------------------------------------------------------------------------------------------------------- 
   Run-In and PK     XX                    XX           X       X         X         X       X         X         X         X      
   Follow-UP         XX                    XX           X       X         X         X       X         X         X         X      
   Overall           XX                    XX           X       X         X         X       X         X         X         X      
   ------------------------------------------------------------------------------------------------------------------------------- 
 
Note: * Adverse events are classified according to MedDRA Version 15.1 
      When a subject experienced the same AE at more than one level of severity during a treatment period, the AE with the maximum 
      severity was counted. When a subject experienced the same AE at more than one level of drug relationship during a treatment 
      period, the most related AE was counted. 
 
 
Program:  /CAXXXXX/sas_prg/stsas/tab_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


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Statistical Analysis Plan 
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Page 53 of 87 
Page 1 of 1 
 
Table 14.3.1.4  Treatment-Emergent Adverse Event Frequency by Severity and Relationship to Drug 
Number of Adverse Events  
 
                                                                                                Relationship to Study Drug 
                                                                                      --------------------------- --------------------- 
                                            Number of         Severity/Intensity      Definitely Probably 
                                           Subjects with    -----------------------   Not        Not      Possibly  Probably 
   Adverse Event*     Phase                Adverse Events   Mild  Moderate  Severe    Related    Related  Related   Related  Definitely 
   ------------------------------------------------------------------------------------------------------------------------------------ 
   Dizziness          Run-In and PK              X           X       X         X         X       X         X         X         X      
                      Follow-Up                  X           X       X         X         X       X         X         X         X      
   Dry eye            Follow-Up                  X           X       X         X         X       X         X         X         X      
   Dry mouth          XXXXXXXXXXXXX              X           X       X         X         X       X         X         X         X      
   Ear pain           XXXXXXXXXXXXX              X           X       X         X         X       X         X         X         X      
                      XXXXXXXXXXXXX              X           X       X         X         X       X         X         X         X      
   Fatigue            XXXXXXXXXXXXX              X           X       X         X         X       X         X         X         X      
   Headache           XXXXXXXXXXXXX              X           X       X         X         X       X         X         X         X      
   Hyperhidrosis      XXXXXXXXXXXXX              X           X       X         X         X       X         X         X         X      
 
   ------------------------------------------------------------------------------------------------------------------------------------ 
   Run-In and PK     XX                         XX           X       X         X         X       X         X         X         X      
   Follow-UP         XX                         XX           X       X         X         X       X         X         X         X      
   Overall           XX                         XX           X       X         X         X       X         X         X         X      
   ------------------------------------------------------------------------------------------------------------------------------------ 
 
Note: * Adverse events are classified according to MedDRA Version 15.1 
 
 
 
 
Program:  /AAXXXXX/sas_prg/stsas/tab_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 
 


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Statistical Analysis Plan 
23 March 2017 
 
Page 54 of 87 
Tables 14.3.2.1 through 14.3.2.3 will have the following format. 
 
Page X of X 
 
Table 14.3.2.1  Serious Adverse Event 
 
                           Adverse Event*              Onset                                                              Relationship  
Subject  Dosing           >Preferred Term          ---------------                Severity/                       Action  to Study      
Number   Day       TE?^  >>System Organ Class      Date       Time  Frequency     Intensity  Serious    Outcome   Taken   Drug          
-------------------------------------------------------------------------------------------------------------------------------------- 
  X      1         Yes     XXXXXXXXXXXXX           DDMMMYYYY  X:XX  Intermittent  Severe     Is life    Unchanged XXXXXX  XXXXXXXXX    
                          >XXXXXXXXXXXXX                                                     threatening 
                         >>XXXXXXXXXXXXXXXXXX 
 
 
 
 
 
 
Programmer Note: if there are no SAEs reported, this table will just show the statement that “No serious adverse event is reported.”. 
 
 
 
 
 
 
 
 
 
 
Note: * Adverse events are classified according to MedDRA Version 15.1. 
 
Program : /CAXXXXX/ECR/sas_prg/stsas/tab/PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 
 
 
 


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Statistical Analysis Plan 
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Page 55 of 87 
Tables 14.3.4.1 through 14.3.4.3 will have the following format. 
 
Page 1 of X 
 
Table 14.3.4.1  Out-of-Range Values and Recheck Results - Chemistry 
 
                Subject           Study                                               Normal  Test                
                Number    Age#    Phase     Day          Date     Parameter   Units   Range   Value   PI Interpretation           
                ----------------------------------------------------------------------------------------------------------------- 
                XXX-XXX    XX     Screen               DDMMMYYYY    XXXXX     XXXX    XX-XX   XXXXX   Not clinically significant  
                                    X       XX         DDMMMYYYY    XXXXX     XXXX    XX-XX   XXXXX   XXXXXXXXXXXXXXXXXXXXXXXXXX  
 
 
 
 
 
 
 
 
Programmer Note: Replace Parameter with actual lab tests in the study. 
 
 
Note: # Age is calculated from the date of informed consent.  
 
 
Program:  /CAXXXXX/sas_prg/stsas/tab_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 
 
 
 


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Statistical Analysis Plan 
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Page 56 of 87 
Tables 14.3.5.1 through 14.3.5.3 will have the following format. 
 
Page 1 of X 
 
Table 14.3.5.1  Clinical Laboratory Summary and Change From Baseline - Chemistry  
 
                    Laboratory Test                                                              Change From  
                    (units)             Study Phase     Day        Statistic                     Baseline     
                    ----------------------------------------------------------------------------------------- 
                    Calcium (mg/dL)     Screening 1                n                  XX    
                                                                   Mean             X.XX    
                                                                   SD              X.XXX    
                                                                   Minimum           X.X    
                                                                   Median           X.XX    
                                                                   Maximum          XX.X    
 
                                        Run-In Phase     1         n                  XX             XX       
                                                                   Mean             X.XX           X.XX       
                                                                   SD              X.XXX          X.XXX       
                                                                   Minimum           X.X            X.X       
                                                                   Median           X.XX           X.XX       
                                                                   Maximum          XX.X           XX.X       
 
                                        PK Phase         1         n                  XX             XX       
                                                                   Mean             X.XX           X.XX       
                                                                   SD              X.XXX          X.XXX       
                                                                   Minimum           X.X            X.X       
                                                                   Median           X.XX           X.XX       
                                                                   Maximum          XX.X           XX.X       
 
Programmer Note: Laboratory tests will be performed at Run-In Phase Day 1, PK Phase Day 1, following the 24-hour PK blood draw on PK Phase 
Day 6, and 5 to 7 days post last dose during the Safety Follow-Up Phase, if the subject needed to return to the clinic for an in person 
visit, or at Early Termination from the study. Screening 1 values will serve as baseline. Subjects will only return for clinical lab 
assessment during the Safety Follow-up Phase if there is a specific need. Therefore, clinical labs will not be summarized for the Safety 
Follow-up visit. 
  
Note:  Refer to Appendix 16.1.10.1 for normal ranges for the laboratory tests. 
 
 
 
Program:  /AAXXXXX/sas_prg/stsas/tab_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 
 


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Statistical Analysis Plan 
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Page 1 of X 
 
Table 14.3.5.4  Vital Sign Summary  
 
                                                                                                         
                                                                                                         
                              Measurement (units)   Study Phase       Day       Statistic                
                              -------------------------------------------------------------------------- 
                              Systolic Blood        Screening 1                 n                XX 
                              Pressure (mmHg)                                   Mean           X.XX 
                                                                                SD            X.XXX 
                                                                                Minimum         X.X 
                                                                                Median         X.XX 
                                                                                Maximum        XX.X 
 
                                                    Run-In Phase       1        n                XX 
                                                                                Mean           X.XX 
                                                                                SD            X.XXX 
                                                                                Minimum         X.X 
                                                                                Median         X.XX 
                                                                                Maximum        XX.X 
 
                                                    PK Phase           1        n                XX      
                                                                                Mean           X.XX      
                                                                                SD            X.XXX      
                                                                                Minimum         X.X      
                                                                                Median         X.XX      
                                                                                Maximum        XX.X      
 
Programmer Note: Blood pressure and heart rate will be measured at Screening 1, Run-In Phase Day 1, and prior to dosing during the PK Phase 
on Days 1, 2, 3, 4, 5, and 6, and 5 to 7 days post last dose during the Safety Follow-Up Phase, if a clinical visit is required for the 
safety follow up, or at Early Termination. Respiration rate and temperature will be measured only at Screening 1 and Early Termination. 
Therefore, no post-dose summaries will be provided for respiration and temperature. Subjects will only return for vital signs assessment 
during the Safety Follow-up Phase if there is a specific need. Therefore, vital signs will not be summarized for the Safety Follow-up visit. 
 
 
 
 
 
Program:  /AAXXXXX/sas_prg/stsas/tab_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


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Statistical Analysis Plan 
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Page 58 of 87 
Page 1 of X 
 
Table 14.3.5.5  Vital Sign Change From Baseline  
 
                                                                            Change From Baseline* 
                                              -------------------------------------------------------------------------------- 
        Measurement (units)                    Run-In   PK Phase   PK Phase   PK Phase   PK Phase   PK Phase   PK Phase        
                                Statistic       Day 1      Day 1      Day 2      Day 3      Day 4      Day 5      Day 6        
        ---------------------------------------------------------------------------------------------------------------------- 
        Systolic Blood          n                  XX         XX         XX         XX         XX         XX         XX        
        Pressure (mmHg)         Mean             X.XX       X.XX       X.XX       X.XX       X.XX       X.XX       X.XX        
                                SD              X.XXX      X.XXX      X.XXX      X.XXX      X.XXX      X.XXX      X.XXX        
                                Minimum           X.X        X.X        X.X        X.X        X.X        X.X        X.X        
                                Median           X.XX       X.XX       X.XX       X.XX       X.XX       X.XX       X.XX        
                                Maximum          XX.X       XX.X       XX.X       XX.X       XX.X       XX.X       XX.X        
 
 
Programmer Note: Blood pressure and heart rate will be measured at Screening 1, Run-In Phase Day 1, and prior to dosing during the PK Phase 
on Days 1, 2, 3, 4, 5, and 6, and 5 to 7 days post last dose during the Safety Follow-Up Phase, if a clinical visit is required for the 
safety follow up, or at Early Termination. Respiration rate and temperature will be measured only at Screening 1 and Early Termination. 
Therefore, no post-dose summaries will be provided for respiration and temperature. Subjects will only return for vital signs assessment 
during the Safety Follow-up Phase if there is a specific need. Therefore, change from baseline will not be calculated for the Safety Follow-
up visit. 
 
 
Note: * Baseline is the average of the triplicate values, including rechecks, measured at Predose Day 1 of the Run-In Phase 
 
Program:  /AAXXXXX/sas_prg/stsas/tab_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 
 


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Statistical Analysis Plan 
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Page 59 of 87 
10. LISTING SHELLS 
The following listing shells provide a framework for the display of data from this 
study. The shells may change due to unforeseen circumstances. These shells may not 
be reflective of every aspect of this study, but are intended to show the general layout 
of the listings that will be presented and included in the final report.  
 


Clarus Therapeutics, Inc. 
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Statistical Analysis Plan 
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Page 1 of X 
 
Appendix 16.1.10.1  Clinical Laboratory Reference Ranges 
 
               Laboratory Group           Test Name                     Gender      Age Category  Normal Range    Unit   
               --------------------------------------------------------------------------------------------------------- 
               Chemistry                  Test Name                     XXXXXX      XX            XX – XX         units 
                                          Test Name                     XXXXXX      XX            XX – XX         units 
                                          Test Name                     XXXXXX      XX            XX – XX         units 
                                          Test Name                     XXXXXX      XX            XX – XX         units 
                                          Test Name                     XXXXXX      XX            XX – XX         units 
                                          Test Name                     XXXXXX      XX            XX – XX         units 
 
               Hematology                 Test Name                     XXXXXX      XX            XX – XX         units 
                                          Test Name                     XXXXXX      XX            XX – XX         units 
                                          Test Name                     XXXXXX      XX            XX – XX         units 
                                          Test Name                     XXXXXX      XX            XX – XX         units 
                                          Test Name                     XXXXXX      XX            XX – XX         units 
 
 
 
 
 
Note to Programmer: Two labs were used in this study so please prepare a separate set of reference ranges for each lab. 
 
 
 
 
 
 
 
 
<similar for remaining Laboratory Groups and Test Names> 
 
 
 
Program:  /CAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 


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Statistical Analysis Plan 
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Appendix 16.2.1  Subject Disposition 
 
                                         Site- 
                                         Subject   Study              Completed  
                                         Number    Phase     Date      Study?   Reason for Discontinuation   
                                       ----------------------------------------------------------------------------- 
                                         XXX-XXX   Post   DDMMMYYYY     No      Personal Reason 
                                         XXX-XXX   Post   DDMMMYYYY     Yes    
                                         XXX-XXX   Post   DDMMMYYYY     Yes    
                                         XXX-XXX   Post   DDMMMYYYY     Yes    
                                         XXX-XXX   Post   DDMMMYYYY     Yes    
                                         XXX-XXX   Post   DDMMMYYYY     Yes    
                                         XXX-XXX   Post   DDMMMYYYY     Yes    
                                         XXX-XXX   Post   DDMMMYYYY     Yes    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program:  /CAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


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Statistical Analysis Plan 
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Page 1 of X 
 
Appendix 16.2.4.1  Demographics 
 
Site-                                                                                       Body Mass               I-PSS    Informed   
Subject      Date Of       Age*                                         Height    Weight      Index          I-PSS  QOL       Consent   
Number        Birth       (yrs)    Gender    Race        Ethnicity      (cm)      (kg)      (kg/m^2)  PSA    Score  Score      Date     
--------------------------------------------------------------------------------------------------------------------------------------- 
XXX-XXX     DDMMMYYYY       XX     Male      AAAAAAAA    AAAAAAAAAA      XXX      XX.XX       XX.XX   XX.X   XX.XX    X      DDMMMYYYY 
XXX-XXX     DDMMMYYYY       XX     Male      AAAAAAAA    AAAAAAAAAA      XXX      XX.XX       XX.XX   XX.X   XX.XX    X      DDMMMYYYY 
XXX-XXX     DDMMMYYYY       XX     Male      AAAAAAAA    AAAAAAAAAA      XXX      XX.XX       XX.XX   XX.X   XX.XX    X      DDMMMYYYY 
XXX-XXX     DDMMMYYYY       XX     Male      AAAAAAAA    AAAAAAAAAA      XXX      XX.XX       XX.XX   XX.X   XX.XX    X      DDMMMYYYY 
XXX-XXX     DDMMMYYYY       XX     Male      AAAAAAAA    AAAAAAAAAA      XXX      XX.XX       XX.XX   XX.X   XX.XX    X      DDMMMYYYY 
XXX-XXX     DDMMMYYYY       XX     Male      AAAAAAAA    AAAAAAAAAA      XXX      XX.XX       XX.XX   XX.X   XX.XX    X      DDMMMYYYY 
XXX-XXX     DDMMMYYYY       XX     Male      AAAAAAAA    AAAAAAAAAA      XXX      XX.XX       XX.XX   XX.X   XX.XX    X      DDMMMYYYY 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note:  * Age will be calculated in years between date of birth and informed consent date. 
       PSA = Prostate specific antigen 
       I-PSS = International Prostate Symptom Score 
       QOL = Quality of Life Score 
 
Program:  /CAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


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Statistical Analysis Plan 
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Page 1 of X 
 
Appendix 16.2.4.2.1  Physical Examination (I of II) 
 
          Site- 
          Subject                               Was PE                                                        
          Number   Study Phase      Date        Performed?  HEENT       Skin/Mucosa   Chest       Lungs       Abdomen     Extremities 
          --------------------------------------------------------------------------------------------------------------------------- 
          XXX-XXX  Screening 2      DDMMMYYYY   NA          NORMAL      ABNORMAL*     NORMAL      NORMAL      NORMAL      NORMAL      
                   Run-In, Day 1    DDMMMYYYY   Yes         UNCHANGED   UNCHANGED     CHANGED*    UNCHANGED   UNCHANGED   UNCHANGED   
                   PK Phase Day 6   DDMMMYYYY   Yes         UNCHANGED   UNCHANGED     UNCHANGED   UNCHANGED   UNCHANGED   UNCHANGED   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: HEENT = Head, Eyes, Ears, Nose, Throat 
      * = See Appendix 16.2.4.2.3. Physical Examination Descriptions. 
 
 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


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Statistical Analysis Plan 
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Appendix 16.2.4.2.2  Physical Examination (II of II) 
 
          Site- 
          Subject                               Was PE      Lymph      Neuro-     Musculo-                       
          Number   Study Phase      Date        Performed?  Nodes      logical    skeletal   Urinary    Rectal      Other     Specify 
          ----------------------------------------------------------------------------------------------------------------------------------- 
          XXX-XXX  Screening 2      DDMMMYYYY   NA          NORMAL     ABNORMAL*  NORMAL     NORMAL     NORMAL       
                   Run-In Day 1     DDMMMYYYY   Yes         UNCHANGED  UNCHANGED  CHANGED*   UNCHANGED              NORMAL    XXXXXXXXXXXXX 
                   PK Phase Day 6   DDMMMYYYY   Yes         UNCHANGED  UNCHANGED  UNCHANGED  UNCHANGED              
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note:  * = See Appendix 16.2.4.2.3. Physical Examination Descriptions. 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


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Statistical Analysis Plan 
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Page 1 of X 
 
Appendix 16.2.4.2.3  Physical Examination Descriptions 
 
 Site- 
 Subject                                                                                                                    
 Number   Study Phase  Date        Result    System                 Description or Comment                                  
 -------------------------------------------------------------------------------------------------------------------------- 
 XXX-XXX  Screening 2  DDMMMYYYY   ABNORMAL   Skin                  RIGHT CHEST SCAR-NCS                                    
                                                                                                                            
 XXX-XXX  Screening 2  DDMMMYYYY   ABNORMAL   Skin                  ABDOMINAL SCAR-NCS                                      
                                                                                                                            
 XXX-XXX  Screening 2  DDMMMYYYY   ABNORMAL   Skin                  ABDOMINAL SCAR-NCS                                      
                                                                                                                            
 XXX-XXX  Screening 2  DDMMMYYYY   ABNORMAL   Skin                  ABDOMINAL SCAR-NCS                                      
                                                                                                                            
 XXX-XXX  Screening 2  DDMMMYYYY   ABNORMAL   Back                  MILD SCOLIOSIS-NCS                                      
                                                                                                                            
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note:  HEENT = Head, Eyes, Ears, Nose, Throat. 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 
 


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Statistical Analysis Plan 
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Page 1 of X 
 
Appendix 16.2.4.3  Medical and Surgical History 
 
            Site-                                      Date 
            Subject                           ------------------------                                       
            Number     Any History?             Start         End        Ongoing?    Description             
            ------------------------------------------------------------------------------------------------ 
            XXX-XXX    YES                      DDMMMYYYY                 YES        XXXXXXX XXXXXX XXXXXXXX 
                                                DDMMMYYYY    DDMMMYYYY    NO         XXXXXXX XXXXXX XXXXXXXX 
            XXX-XXX    YES                      DDMMMYYYY    DDMMMYYYY    NO         XXXXXXX XXXXXX XXXXXXXX   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note:  NA = Not Applicable 
 
Program:  /CAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


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Statistical Analysis Plan 
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Appendix 16.2.4.4  Testosterone Replacement Therapy - Screening 
 
               Site-     Received                              Date                                            
               Subject   Prior                          -----------------------                                           
               Number    Therapy?   Medication          Start         End             Dose    Unit    Frequency    Route  
               ---------------------------------------------------------------------------------------------------------- 
               XXX-XXX   Yes        XXXXXX  XXXXX       DDMMMYYYY     DDMMMYYYY       XXXX    XXXX    XXXXX        Oral   
               XXX-XXX   No                                                                                               
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program:  /CAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 
 


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Appendix 16.2.4.5  Hypogonadism Signs and Symptoms - Screening 
 
Site- 
Subject  
Number    Date      Signs and Symptoms                                                                                        Response 
-------------------------------------------------------------------------------------------------------------------------------------- 
XXX-XXX   DDMMMYYY  Incomplete sexual development, eunochoidism                                                                Yes    
                    Reduced sexual desire (libido) and activity                                                                Yes    
                    Decreased spontaneous erections                                                                            Yes    
                    XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX                                                                         Yes    
 
 
 
 
Note to programmer: There are 18 signs and symptoms to list for each subject in the CRF. But in this listing present only those which are 
responded to with YES. 
 
 
 
 
 
 
 
 
 
Program:  /CAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 
 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
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Statistical Analysis Plan 
23 March 2017 
 
Page 69 of 87 
Page 1 of X 
 
Appendix 16.2.4.6  International Prostate Symptom Score (I-PSS) and Quality of Life Due to Urinary Symptoms Score - Screening 
 
Site- 
Subject  
Number    Date      Symptom                                                                                                           Score  
-------------------------------------------------------------------------------------------------------------------------------------------- 
XXX-XXX   DDMMMYYY  1. Over the past month, how often have you had a sensation of not emptying your bladder completely after you  
                       finished urinating?                                                                                              X 
                    2. Over the past month, how often have you had to urinate again less than two hours after you finished urinating?   X 
                    3. Over the past month, how often have you found you stopped and started again several times when you urinated?     X 
                    4. Over the past month, how often have you found it difficult to postpone urination?                                X 
                    5. Over the past month, how often have you had a weak urinary stream?                                               X 
                    6. Over the past month, how often have you had to push or strain to begin urination?                                X 
                    7. Over the past month, how many times did you most typically get up to urinate from the time you went to bed at      
                       night until the time you got up in the morning?                                                                  X 
                    Total I-PSS Score                                                                                                  XX 
                    8. If you were to spend the rest of your life with your urinary condition just the way it is now, how would you  
                       feel about that?                                                                                                 X 
 
 
Note: The Total I-PSS score is the sum of the first 7 questions.  
 
 
 
 
 
 
 
 
 
Program:  /CAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 70 of 87 
Page 1 of X 
 
Appendix 16.2.5.2  Subject Eligibility 
 
 Site- 
 Subject  Study              Did subject meet                                                          
 Number   Phase         all eligibility criteria?     Criterion Not Met*     Specify                   
------------------------------------------------------------------------------------------------------ 
 XXX-XXX  Screening 1             Yes                                                                  
          Screening 2             No                  EXCLUSION X            XXXXXXXXXXXXXXX XXXX      
 XXX-XXX  Screening 1             Yes                                                                  
          Screening 2             Yes                                                                  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program:  /CAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM  
 
 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 71 of 87 
Page 1 of X 
 
Appendix 16.2.5.3  Dosing - Run-In Phase Days 1 and 14 
 
                                    Site- 
                                    Subject           Time-   
                                    Number     Day    point  Administered? Date        Time      Compound    
                                    ------------------------------------------------------------------------ 
                                    XXX-XXX     1      AM    Yes           DDMMMYYYY   HH:MM     XXXXXXXXX   
                                               14      PM    Yes           DDMMMYYYY   HH:MM     XXXXXXXXX   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program:  /CAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 72 of 87 
Page 1 of X 
 
Appendix 16.2.5.4  Dose Accountability – Run-In Phase Days 1-14 
 
Site-                                   AM Time                 PM Time                   Capsules  
Subject                            -----------------       -------------------    ---------------------- 
Number     Day         Date        Dosing      Meal        Dosing      Meal       Dispensed     Returned 
-------------------------------------------------------------------------------------------------------- 
XXX-XXX     1          DDMMMYYYY                           HH:MM       HH:MM         XX 
            2          DDMMMYYYY   HH:MM       HH:MM       HH:MM       HH:MM  
            3          DDMMMYYYY   HH:MM       HH:MM       HH:MM       HH:MM  
            4          DDMMMYYYY   HH:MM       HH:MM       HH:MM       HH:MM  
            5          DDMMMYYYY   HH:MM       HH:MM       HH:MM       HH:MM  
            6          DDMMMYYYY   HH:MM       HH:MM       HH:MM       HH:MM  
            7          DDMMMYYYY   HH:MM       HH:MM       HH:MM       HH:MM  
            8          DDMMMYYYY   HH:MM       HH:MM       HH:MM       HH:MM  
            9          DDMMMYYYY   HH:MM       HH:MM       HH:MM       HH:MM  
           10          DDMMMYYYY   HH:MM       HH:MM       HH:MM       HH:MM  
           11          DDMMMYYYY   HH:MM       HH:MM       HH:MM       HH:MM  
           12          DDMMMYYYY   HH:MM       HH:MM       HH:MM       HH:MM  
           13          DDMMMYYYY   HH:MM       HH:MM       HH:MM       HH:MM  
           14          DDMMMYYYY   HH:MM       HH:MM                                             XX 
 
 
 
 
 
 
 
 
 
 
 
 
Program:  /CAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 73 of 87 
Page 1 of X 
 
Appendix 16.2.5.5  Dosing – PK Phase  
 
                                              Site- 
                                              Subject   Time-  Dose  
                                              Number    point  Administered? Date        Time      Compound   
                                              --------------------------------------------------------------- 
                                              XXX-XXX    AM    Yes           DDMMMYYYY   HH:MM     XXXXXXXXX  
                                                         PM    Yes           DDMMMYYYY   HH:MM     XXXXXXXXX  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program:  /CAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 74 of 87 
Page 1 of X 
 
Appendix 16.2.5.6  Blood Draw Times 
 
                  Site- 
                  Subject  Study                                                 
                  Number   Phase    Day        Hour     Date       Time      Bioassay          Comments                  
                  ------------------------------------------------------------------------------------------------------ 
                  XXX-XXX    X       XX       -X.XX  DDMMMYYYY     XX:XX     XXXXXXXXXX                                  
                                               X.XX  DDMMMYYYY     XX:XX     XXXXXXXXXX                                  
                                               X.XX  DDMMMYYYY     XX:XX     XXXXXXXXXX                                  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program:  /CAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 
 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 75 of 87 
Page 1 of X 
Appendix 16.2.5.7  Meal Times 
 
 Site- 
 Subject     Study             Meal                             Start     Stop     Entire Mean                  
 Number      Phase      Day    Plan     Event       Date        Time      Time     Consumed?     Comments       
 -------------------------------------------------------------------------------------------------------------- 
 XXX-XXX     PK Phase   X       X       Breakfast   DDMMMYYYY   XX:XX:XX  XX:XX:XX    Yes                       
                                        Dinner      DDMMMYYYY   XX:XX:XX  XX:XX:XX    Yes 
                                X       Breakfast   DDMMMYYYY   XX:XX:XX  XX:XX:XX    No             75% 
                                        Dinner      DDMMMYYYY   XX:XX:XX  XX:XX:XX    Yes 
                                X       Breakfast   DDMMMYYYY   XX:XX:XX  XX:XX:XX    Yes                       
                                        Dinner      DDMMMYYYY   XX:XX:XX  XX:XX:XX    Yes                       
 
 
 
 
Note to Programmer: If the subject received Meal Plan A (fasting for breakfast) the Start Time, Stop Time, and Entire Mean Consumed? will be 
blank. 
 
 
 
 
 
 
 
 
Meal Plan 
A: Fasting condition for breakfast 
B: 15 g fat breakfast 
C: 30 g fat breakfast 
D: 45 g fat breakfast 
E: FDA high-calorie, high-fat breakfast 
 
 
 
Program:  /CAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 76 of 87 
Page 1 of X 
 
Appendix 16.2.5.8.1 Prior Medications 
 
Site- 
Subject   Any    Medication                                                    Start     Start   Stop      Stop              
Number    Med?    (WHO* Term)     Indication  Dose  Unit  Route   Frequency    Date      Time    Time      Date  Continuing? 
---------------------------------------------------------------------------------------------------------------------------- 
XXX-XXX   No     None                                                                                                        
XXX-XXX   Yes    ACETAMINOPHEN    Toothache   620   MG    ORAL    Once         DDMMMYYYY HH:MM   DDMMMYYYY HH:MM    No       
                  (ACETAMINOPHEN) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Prior medications include any medication begun prior to first dose of study medication. 
      Prior medications are coded with the WHO Dictionary Version SEP2012 
 
 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 77 of 87 
Page 1 of X 
 
Appendix 16.2.5.8.2 Concomitant Medications 
 
Site- 
Subject  Any    Medication                   Associated                                       Start     Start   Stop      Stop  Continuing   
Number   Med?    (WHO* Term)     Indication  AE Number       Dose  Unit  Route   Frequency    Date      Time    Time      Date  Medication?  
 ------------------------------------------------------------------------------------------------------------------------------------------- 
XXX-XXX  No     None                                                                                                                         
XXX-XXX  Yes    ACETAMINOPHEN    Toothache   XXXXXXXXX       620   MG    ORAL    Once         DDMMMYYYY HH:MM   DDMMMYYYY HH:MM    No        
                 (ACETAMINOPHEN) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note:  Concomitant medications are coded with the WHO Dictionary Version SEP2012 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 78 of 87 
 Page 1 of X 
 
Appendix 16.2.7.1  Adverse Events (I of II) 
 
                                                                            Time From                                                 
Site-                                                                       Last Dose       Onset           Resolved       Duration   
Subject  Study                                                              ---------- ---------------   --------------   ----------- 
Number   Phase   Day    TE?^   Adverse Event*       Preferred Term          (DD:HH:MM) Date       Time   Date       Time  (DD:HH:MM)  
------------------------------------------------------------------------------------------------------------------------------------- 
XXX-XXX                        None                                                                                                   
          X      XX     Yes    XXXXXXXXXXXXX        XXXXXXXXXX XXXXXXX       XX:XX:XX  DDMMMYYYY  X:XX   DDMMMYYYY  X:XX   XX:XX:XX   
 
 
 
 
 
 
 
 
 
 
 
 
Note:  ^ = Abbreviation for treatment-emergent. An AE is considered treatment-emergent if it begins or worsens in severity after the first 
dose of the study drug.  
     * = Adverse events are classified according to MedDRA Version 15.1. 
 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 79 of 87 
Page 1 of X 
 
Appendix 16.2.7.2  Adverse Events (II of II) 
 
                                                                                                                Relation-             
    Site-                                                  Onset                                                ship to               
    Subject  Study               Adverse              ---------------                                           Study      Action     
    Number   Phase     Day       Event                  Date    Time  Frequency     Severity Serious Outcome    Drug       Taken      
    --------------------------------------------------------------------------------------------------------------------------------- 
    XXX-XXX                      None                                                                                       
              X         XX       XXXXXXXXXXXXXXXXXX  DDMMMYYYY  XX:XX Intermittent  Mild     Yes/No  Resolved   XXXXXXXX   None       
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note:  ^ = Abbreviation for treatment-emergent. An AE is considered treatment-emergent if it begins or worsens in severity after the first 
dose of the study drug.  
      * = Adverse events are classified according to MedDRA Version 15.1. 
 
 
 
Program:  /CAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 
 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 80 of 87 
Appendices 16.2.8.1 to 16.2.8.3 will have the following format. 
Page 1 of X 
 
Appendix 16.2.8.1  Clinical Laboratory Report - Chemistry 
 
     Site-                                                  Parameter1  Parameter2   Parameter3    Parameter4  Parameter5 Parameter6  
     Subject          Study                                 < Range>    < Range>     < Range>      < Range>    < Range>   < Range>     
     Number    Age    Phase      Day              Date       (Unit)      (Unit)       (Unit)        (Unit)      (Unit)     (Unit)      
     --------------------------------------------------------------------------------------------------------------------------------- 
     XXX-XXX    XX    Screen                    DDMMMYYYY      XX HN       XX           XX            XX          XX         XX        
                XX    Post       XX             DDMMMYYYY      XX LY       XX           XX            XX          XX         XX        
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmer Note: Replace Parameter1, 2 etc. with actual lab tests in the study. Sort unscheduled assessment and early term chronologically 
with other scheduled assessments and rechecks.  Recheck should be sorted with the scheduled timepoint the recheck is for. 
 
 
 
 
 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM  
 
 
 
 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 81 of 87 
Page 1 of X 
 
Appendix 16.2.8.4  Clinical Laboratory Report – Total Testosterone and DHT 
 
                    Site-                                                 Total         Dihydro-       
                    Subject          Study                                Testosterone  testosterone   
                    Number    Age    Phase          Day         Date       (Unit)        (Unit)        
                    ---------------------------------------------------------------------------------- 
                    XXX-XXX    XX    Screening 1              DDMMMYYYY      XXX                       
                                     Screening 2              DDMMMYYYY      XXX                       
                                     Run-In          1        DDMMMYYYY      XXX           XXX         
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmer Note: Replace Parameter1, 2 etc. with actual lab tests in the study. Sort unscheduled assessment and early term chronologically 
with other scheduled assessments and rechecks.  Recheck should be sorted with the scheduled timepoint the recheck is for. 
 
 
 
 
 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM  
 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 82 of 87 
Page 1 of X 
 
Appendix 16.2.8.5  Clinical Laboratory Report - Comments 
 
 Site- 
 Subject Study                                                                                                           
 Number  Phase   Day         Date    Department         Test         Result       Unit      Comment                      
 ----------------------------------------------------------------------------------------------------------------------- 
 XXX-XXX   X     XX        DDMMMYYYY  Serum Chemistry   Calcium       XXX          mg/dL     Not significant in the      
                                                                                             context of this study.      
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program:  /CAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 83 of 87 
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Appendix 16.2.8.6  Vital Signs 
 
Site-                                             Blood Pressure (mmHg)     Heart Respir-  Temper-                          
Subject Study                                    -----------------------    rate  ation    ature   Height   Weight  BMI     
Number  Phase         Day       Date       Time  Arm  Systolic/Diastolic    (bpm) (rpm)    (°C)    (cm)     (kg)  (kg/cm2)  
--------------------------------------------------------------------------------------------------------------------------- 
XXX-XXX Screening 1             DDMMMYYYY  XX:XX Left       XXX/ XX         XX    XX       XX.X    XXX.X    XXX.X   XXX.X   
                                DDMMMYYYY  XX:XX Left       XXX/ XX         XX                                              
                                DDMMMYYYY  XX:XX Left       XXX/ XX         XX                                              
        Run-In        1         DDMMMYYYY  XX:XX Left       XXX/ XX         XX                                              
                                DDMMMYYYY  XX:XX Left       XXX/ XX         XX                                              
                                DDMMMYYYY  XX:XX Left       XXX/ XX         XX                                              
        PK Phase      1         DDMMMYYYY  XX:XX XXXX       XXX/ XX         XX                                              
                                DDMMMYYYY  XX:XX XXXX       XXX/ XX         XX                                              
                               DDMMMYYYY  XX:XX XXXX       XXX/ XX         XX                                              
 
 
 
 
 
 
Programmer note: Sort unscheduled assessment and early term chronologically with other scheduled assessments. 
 
 
 
 
 
 
 
 
 
Program:  /CAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 84 of 87 
Page 1 of X 
 
Appendix 16.2.8.7  Vital Signs – Average of Triplicate Values 
 
Site-                                             Blood Pressure (mmHg)     Heart   
Subject Study                                    -----------------------    rate    
Number  Phase         Day       Date       Time  Arm  Systolic/Diastolic    (bpm)   
----------------------------------------------------------------------------------- 
XXX-XXX Screening 1             DDMMMYYYY  XX:XX Left       XXX/ XX         XX      
        Run-In        1         DDMMMYYYY  XX:XX Left       XXX/ XX         XX      
        PK Phase      1         DDMMMYYYY  XX:XX XXXX       XXX/ XX         XX      
        PK Phase      2         DDMMMYYYY  XX:XX XXXX       XXX/ XX         XX      
        PK Phase      3        DDMMMYYYY  XX:XX XXXX       XXX/ XX         XX      
        PK Phase      4         DDMMMYYYY  XX:XX XXXX       XXX/ XX         XX      
        PK Phase      5         DDMMMYYYY  XX:XX XXXX       XXX/ XX         XX      
        PK Phase      6        DDMMMYYYY  XX:XX XXXX       XXX/ XX         XX      
 
 
 
 
 
Programmer note: Sort unscheduled assessment and early term chronologically with other scheduled assessments. 
 
 
 
 
 
 
 
 
 
Program:  /CAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 85 of 87 
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Appendix 16.2.8.8  Phone Call – Safety Follow-Up Phase 
 
       Site- 
       Subject                                                              Has subject experienced any clinically  
       Number    Date       Was phone call made?                            significant changes in health?               Comments 
       -------------------------------------------------------------------------------------------------------------------------- 
       XXX-XXX   DDMMMYYY   No, subject returned for follow-up visit        Yes/No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program:  /AAXXXXX/sas_prg/stsas/lis_PROGRAMNAME.sas  DDMMMYYYY  HH:MM 
 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 86 of 87 
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Appendix 16.2.8.9  Study Completion/Early Termination 
 
                 Site-      Subject     Competion/         
                 Subject    Complete    Discontinuation   Date of                        
                 Number     Study       Date              Last Dose   Reason             
                 ------------------------------------------------------------------------------------------------- 
                 XXX-XXX    Yes         DDMMMYYYY         DDMMMYYYY    
                 XXX-XXX    No          DDMMMTTTT         DDMMMYYYY   XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
 
 
 
 


Clarus Therapeutics, Inc. 
CLAR-16015 
Celerion, Clinical Study Report No. CA20804 
 
Statistical Analysis Plan 
23 March 2017 
 
Page 87 of 87 
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Appendix 16.2.8.10  General Comments 
 
                 Site- 
                 Subject    
                 Number    Any Comments?  Date        Page #    Comment            
                 ------------------------------------------------------------------------------------------ 
                 XXX-XXX   None 
                 XXX-XXX                  DDMMMYYYY    XX       XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
                 XXX-XXX                  DDMMMYYYY    XX       XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX