Clinical trial NCT03335254
Conditions: Hypogonadism Hypogonadism, Male Gonadal Disorders Endocrine System Diseases Testosterone Deficiency
Keywords: Hypogonadism Testosterone Testosterone undecanoate
Sponsor: TesoRx Pharma, LLC
Start date: 2017-11-06; Completion date: 2018-05-03
Enrollment: 9 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This will be a phase 1/2a, open-label, single-center study with 3 periods. The aims of the study are to:

1. evaluate the dose-response curve following ascending single doses of TSX-011;
2. confirm optimum dosing conditions;
3. evaluate the efficacy of single or multiple daily adaptive dosing; and
4. evaluate the safety and tolerability of TSX-011.

Detailed description:
This will be a phase 1/2a, open-label, single-center study with 3 periods. The aims of the study are to: 1) evaluate the dose-response curve following ascending single doses of TSX-011; 2) confirm optimum dosing conditions; 3) evaluate the efficacy of single or multiple daily adaptive dosing; and 4) evaluate the safety and tolerability of TSX-011. Up to 24 hypogonadal men will be enrolled in this study to yield 16 evaluable subjects, and it is desired that the same 24 subjects participate in all 3 study periods.

Period 1 is an ascending single-dose study of TSX-011 at 3 doses, with the lowest dose administered under fed and fasted conditions: 190 mg TSX-011 in the fed state, 190 mg TSX-011 in the fasted state, 380 mg TSX-011 in the fed state, and 570 mg TSX-011 in the fed state. Before exposure to TSX-011, a 24 hour baseline measurement of testosterone and DHT will be performed for each subject. Samples for analysis of testosterone will be obtained at the following time points on Day -1: hour 0 (8 am ± 60 minutes) and 1.5, 3, 4.5, 6, 8, 12, 16, and 24 hours (± 15 minutes for each time point).

The day following the sampling for endogenous testosterone (Day 1) in Period 1, each subject will receive the first single dose of TSX-011 (190 mg) under fed conditions. Following administration of TSX-011, blood samples will be obtained over a 24-hour period for PK analysis. Subjects will undergo a minimum 3-day and up to 7-day washout period between each of the doses of TSX-011 in Period 1. After the 570 mg TSX 011 dose in Period 1, a minimum 3-day and up to 7-day washout period will occur before the start of Period 2.

Period 2 is a twice-daily dosing period, where fed subjects will be dosed with 380 mg TSX-011 twice daily for 15 days (Days 1 through 15). Pharmacokinetic assessments over 24 hours will occur on Days 1 and 15. The TSX-011 dose will be titrated up or down beginning with the Day 16 (Period 3) morning dose, based on established dosing rules.

Period 3 is a dose-adjusted adaptive design period that begins on Day 16, with the first adjusted TSX-011 dose administered in the fed state on a once-daily or twice-daily schedule. The 6-hour postdose (± 15 minutes) testosterone level on Day 19 will be used to perform the second and final TSX-011 dose adjustment, based on established criteria. As specified by the dose adjustment rules, Day 26 begins with either a once-daily, twice-daily, or thrice-daily fed dose schedule. The thrice-daily dose schedule will be administered only to non-responders. On Day 30, a 24 hour PK assessment will be performed, and the subject's participation in the study is completed the morning of Day 31.

Arms: arm 1: Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed).

Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is \<350 ng/dL, adjust dose to 570 mg (TU) TSX-011 twice daily.

Period 3, Day 26-30: Thrice Daily Dose If Period 3 Day 19 total testosterone is \<350 ng/dL, dose adjust subjects to 570 mg TSX-011 (TU) dosing thrice daily.

Assigned Intervention: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient. arm 2: Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed).

Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is \<350 ng/dL, adjust dose to 570 mg (TU) TSX-011 twice daily.

Period 3, Day 26-30: Twice Daily Dose If Period 3 Day 19 total testosterone is ≥350 ng/dL and \<500 ng/dL, adjust dose to 633 mg TU twice daily.

TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient. arm 3: Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed).

Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is \<350 ng/dL, adjust dose to 570 mg (TU) TSX-011 twice daily.

Period 3, Day 26-30: Twice Daily Dose If Period 3 Day 19 total testosterone is 500 to 800 ng/dL inclusive, continue current dose 570 mg (TU) TSX-011 twice daily.

TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient. arm 4: Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed).

Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is \<350 ng/dL, adjust dose to 570 mg (TU) TSX-011 twice daily.

Period 3, Day 26-30: Twice Daily Dose If Period 3 Day 19 total testosterone is \>800 ng/dL, decrease to 507 mg TU twice daily.

TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient. arm 5: Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed).

Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is ≥350 ng/dL and \<500 ng/dL, adjust dose to 443 mg (TU) TSX-011 twice daily.

Period 3, Day 26-30: Thrice Daily Dose If Period 3 Day 19 total testosterone is \<350 ng/dL, dose adjust subjects to 570 mg TSX-011 (TU) dosing thrice daily.

TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient. arm 6: Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed).

Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is ≥350 ng/dL and \<500 ng/dL, adjust dose to 443 mg (TU) TSX-011 twice daily.

Period 3, Day 26-30: Twice Daily Dose If Period 3 Day 19 total testosterone is ≥350 ng/dL and \<500 ng/dL, adjust dose to 507 mg TU twice daily.

TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient. arm 7: Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed).

Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is ≥350 ng/dL and \<500 ng/dL, adjust dose to 443 mg (TU) TSX-011 twice daily.

Period 3, Day 26-30: Twice Daily Dose If Period 3 Day 19 total testosterone is 500 to 800 ng/dL inclusive, continue current dose 443 mg (TU) TSX-011 twice daily.

TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient. arm 8: Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed).

Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is ≥350 ng/dL and \<500 ng/dL, adjust dose to 443 mg (TU) TSX-011 twice daily.

Period 3, Day 26-30: Twice Daily Dose If Period 3 Day 19 total testosterone is \>800 ng/dL, decrease dose to 380 mg TU twice daily.

TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient. arm 9: Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed).

Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is 500 to 800 ng/dL, inclusive, maintain 380 mg (TU) TSX-011 twice daily.

Period 3, Day 26-30: Thrice Daily Dose If Period 3 Day 19 total testosterone is \<350 ng/dL, dose adjust subjects to 570 mg TSX-011 (TU) dosing thrice daily.

TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient. arm 10: Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed).

Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is 500 to 800 ng/dL, inclusive, maintain 380 mg (TU) TSX-011 twice daily.

Period 3, Day 26-30: Twice Daily Dose If Period 3 Day 19 total testosterone is ≥350 ng/dL and \<500 ng/dL, increase dose to 443 mg TU twice daily.

TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient. arm 11: Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed).

Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is 500 to 800 ng/dL, inclusive, maintain 380 mg (TU) TSX-011 twice daily.

Period 3, Day 26-30: Twice Daily Dose If Period 3 Day 19 total testosterone is 500 to 800 ng/dL inclusive, continue current dose 380 mg (TU) TSX-011 twice daily.

TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient. arm 12: Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed).

Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is 500 to 800 ng/dL, inclusive, maintain 380 mg (TU) TSX-011 twice daily.

Period 3, Day 26-30: Twice Daily Dose If Period 3 Day 19 total testosterone is \>800 ng/dL, decrease TSX-011 dose to 317 mg TU twice daily.

TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient. arm 13: Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed).

Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is \>800 ng/dL, randomize half subjects to receive 317 mg (TU) TSX-011 twice daily Period 3, Day 26-30: Thrice Daily Dose If Period 3 Day 19 total testosterone is \<350 ng/dL, dose adjust subjects to 570 mg TSX-011 (TU) dosing thrice daily.

TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient. arm 14: Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed).

Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is \>800 ng/dL, randomize half subjects to receive 317 mg (TU) TSX-011 twice daily.

Period 3, Day 26-30: Twice Daily Dose If Period 3 Day 19 total testosterone is ≥350 ng/dL and \<500 ng/dL, increase dose to 380 mg TU twice daily.

TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient. arm 15: Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed).

Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is \>800 ng/dL, randomize half subjects to receive 317 mg (TU) TSX-011 twice daily.

Period 3, Day 26-30: Twice Daily Dose If Period 3 Day 19 total testosterone is 500 to 800 ng/dL inclusive, continue current dose 317 mg (TU) TSX-011 twice daily.

TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient. arm 16: Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed).

Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is \>800 ng/dL, randomize half subjects to receive 317 mg (TU) TSX-011 twice daily.

Period 3, Day 26-30: Twice Daily Dose If Period 3 Day 19 total testosterone is \>800 ng/dL, decrease dose to 253 mg TU twice daily.

TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient. arm 17: Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed).

Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Once Daily Dose If Period 2 Day 8 total testosterone is \>800 ng/dL, randomize half subjects to receive 507 mg (TU) TSX-011 once daily.

Period 3, Day 26-30: Thrice Daily Dose If Period 3 Day 19 total testosterone is \<350 ng/dL, dose adjust subjects to 570 mg TSX-011 (TU) dosing thrice daily.

TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient. arm 18: Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed).

Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Once Daily Dose If Period 2 Day 8 total testosterone is \>800 ng/dL, randomize half subjects to receive 507 mg (TU) TSX-011 once daily.

Period 3, Day 26-30: Once Daily Dose If Period 3 Day 19 total testosterone is ≥350 ng/dL and \<500 ng/dL, dose adjust subjects on once-daily dosing from 507 mg TU daily to 570 mg TU daily.

TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient. arm 19: Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed).

Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Once Daily Dose If Period 2 Day 8 total testosterone is \>800 ng/dL, randomize half subjects to receive 507 mg (TU) TSX-011 once daily.

Period 3, Day 26-30: Once Daily Dose If Period 3 Day 19 total testosterone is 500 to 800 ng/dL inclusive, continue current dose of 507 mg TU daily.

TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient. arm 20: Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed).

Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Once Daily Dose If Period 2 Day 8 total testosterone is \>800 ng/dL, randomize half subjects to receive 507 mg (TU) TSX-011 once daily.

Period 3, Day 26-30: Once Daily Dose If Period 3, Day 19 total testosterone is \>800 ng/dL, decrease dose to 380 mg TU daily.

TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.
Interventions: intervention 1: TSX-011
Intervention descriptions: intervention 1: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.

Protocol documents:
Prot_000.pdf: 
A Phase 1/2a Study to Determine the Dose Response 
Pharmacokinetics of TSX-011 (Testosterone Undecanoate) in 
Hypogonadal Males
TesoRx Pharma, LLC
TesoRx Study Number: TT-018
Version: 3.0
Date: 5 March 2018
IND Number 135144
Statement of Confidentiality
The confidential information in this document is provided to you as an investigator or consultant for 
review by you, your staff, and the applicable Institutional Review Board.  Your acceptance of this 
document constitutes agreement that you will not disclose the information contained herein to others
without written authorization from the sponsor.


TLSORA; Pharma. ! LC
Protocol Number TT-OIS
TSJi-OI l Dose Response Study
A PhaseI/2a Study to Determine the Dose Response Pharmacokinetic* of TSX-OlI
(Testosterone Lndeeanoate) in l!_vpogonadal Males,
SIGNATURE PAGE
We, the undersigned, have read this protocol and agree that it contains ail necessary information
required to conduct this study:
Sponsor:
TesoRv Pharma. I..LC
3G70 W Temple Avenue, Suite 270
Pomona. CA 91768. LISA
Sponsor’s
Representative:
5MMcff- 2o®
Michael ti. Oefelcin, MD. FACS
Chief Medical Officer
TesoRx Pharma LLC.
3670 W Temple Avenue, Suite 270
Pomona, CA 91768. USA
Date
Confidential
Page 2


TesoRx Pharma, LLC 
TSX-011 Dose Response Study
Protocol Number: TT-018
Confidential 
Page 3
STUDY CONTACTS AND FACILITIES
SAE Reporting Contact
Michael G. Oefelein, MD
TesoRx Pharma LLC.
3670 W Temple Avenue, Suite 270
Pomona, CA 91768, USA
Phone: 909-595-0500
Fax: 909-468-1222
Sponsor Representative
Chief Executive Officer
Ramachandran Thirucote, PhD
3670 W Temple Avenue, Suite 270
Pomona, CA 91768, USA 


TesoRx Pharma, LLC 
TSX-011 Dose Response Study
Protocol Number: TT-018
Confidential 
Page 4
TABLE OF CONTENTS
SIGNATURE PAGE .......................................................................................................................2
STUDY CONTACTS AND FACILITIES ......................................................................................3
TABLE OF CONTENTS .................................................................................................................4
1.
PROTOCOL SYNOPSIS .............................................................................................7
2.
SCHEDULE OF EVENTS .........................................................................................15
3.
LIST OF ABBREVIATIONS .....................................................................................22
4.
INTRODUCTION ......................................................................................................24
4.1.
Pharmacologic Profile ................................................................................................25
4.2.
Toxicology ..................................................................................................................25
4.3.
Pharmacokinetic Profile ..............................................................................................25
4.4.
Clinical Experience .....................................................................................................26
4.5.
Study Rationale ...........................................................................................................26
5.
STUDY OBJECTIVES ..............................................................................................27
5.1.
Study Objectives .........................................................................................................27
6.
INVESTIGATIONAL PLAN .....................................................................................28
6.1.
Overall Study Design ..................................................................................................28
6.2.
Study Endpoints ..........................................................................................................30
6.3.
Treatments ..................................................................................................................31
6.4.
Stopping Rules of Dose Escalation .............................................................................32
7.
SELECTION, EXCLUSION AND WITHDRAWAL CRITERIA ............................33
7.1.
Inclusion Criteria ........................................................................................................33
7.2.
Exclusion Criteria .......................................................................................................33
7.3.
Subject Withdrawal and Replacement ........................................................................35
8.
STUDY CONDUCT ...................................................................................................36
8.1.1.
Screening ....................................................................................................................36
8.1.2.
Subject Confinement ..................................................................................................37
8.1.3.
Study Duration ............................................................................................................37
9.
TREATMENT OF SUBJECTS ..................................................................................38
9.1.1.
Prohibited Food and Beverages ..................................................................................38
9.1.2.
Prohibited Medications ...............................................................................................39


TesoRx Pharma, LLC 
TSX-011 Dose Response Study
Protocol Number: TT-018
Confidential 
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9.1.3.
Concomitant Medications ...........................................................................................39
9.1.4.
Level of Activity During the Confinement Period .....................................................39
10.
SAFETY ASSESSMENTS ........................................................................................40
10.1.
ECGs ...........................................................................................................................40
10.2.
Vital Signs ..................................................................................................................40
10.3.
Physical Examination .................................................................................................40
10.4.
Clinical Laboratory Tests ...........................................................................................40
10.5.
Adverse Events ...........................................................................................................41
10.5.1.
Definitions of Adverse Events ....................................................................................42
10.5.1.1.
Adverse Event (AE) ....................................................................................................42
10.5.1.2.
Serious Adverse Event (SAE) ....................................................................................42
10.5.1.3.
Serious and Unexpected Suspected Adverse Reactions (SUSARs) ...........................43
10.5.2.
Adverse Event Monitoring .........................................................................................44
10.5.3.
Reporting Adverse Events (AEs), Serious Adverse Events (SAEs) and 
Suspected Unexpected Serious Adverse Reactions (SUSARS) .................................44
10.5.3.1.
Reporting Adverse Event (AEs) .................................................................................44
10.5.3.2.
Reporting Serious Adverse Events (SAEs) ................................................................46
10.5.3.3.
Reporting Suspected Unexpected Serious Adverse Reactions (SUSARS) ................46
10.5.4.
Pregnancy Reporting ..................................................................................................47
11.
PHARMACOKINETIC ASSESSMENTS .................................................................48
11.1.
PK Blood Samples ......................................................................................................48
11.2.
Blood Volume, Pharmacokinetic Blood Sample Processing/ Analysis, and 
Bioanalytical Method ..................................................................................................49
12.
EXPLORATORY ASSESSMENTS ..........................................................................50
13.
STUDY DRUG MATERIALS AND MANAGEMENT ...........................................51
13.1.
Investigational Products ..............................................................................................51
13.2.
Drug Identification ......................................................................................................51
13.3.
Drug Supply ................................................................................................................51
13.4.
Drug Accountability, Storage, and Retention .............................................................51
13.5.
Randomization and Blinding ......................................................................................52
13.5.1.
Randomization:  Based on Day 8 Testosterone Level ................................................52
13.6.
Dosage and Administration ........................................................................................52


TesoRx Pharma, LLC 
TSX-011 Dose Response Study
Protocol Number: TT-018
Confidential 
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13.7.
Meal Schedule ............................................................................................................52
13.8.
Water Administration .................................................................................................53
14.
STATISTICS ..............................................................................................................54
14.1.
Sample Size Calculation .............................................................................................54
14.2.
Analysis Populations ..................................................................................................54
14.3.
Statistical Analyses .....................................................................................................54
14.3.1.
Safety Analyses ..........................................................................................................54
14.4.
Pharmacokinetic Analyses ..........................................................................................55
14.4.1.
Pharmacokinetic Parameters .......................................................................................55
14.4.2.
Method for Baseline-Adjustment of Pharmacokinetic Parameters ............................56
14.4.3.
Pharmacokinetic Data Analyses .................................................................................56
15.
STUDY ADMINISTRATION ...................................................................................57
15.1.
Basic Principles ..........................................................................................................57
15.2.
Data Capture ...............................................................................................................57
15.3.
Study Report ...............................................................................................................57
15.4.
Confidentiality ............................................................................................................57
15.5.
Publication Policy .......................................................................................................57
15.6.
Procedure for Amendments to Protocol .....................................................................57
15.7.
Institutional Review Board .........................................................................................58
15.8.
Termination of Study ..................................................................................................58
15.9.
Study Records .............................................................................................................58
15.10.
Quality Assurance/Quality Control ............................................................................58
16.
REFERENCES ...........................................................................................................59
APPENDIX 1.
INTERNATIONAL PROSTATE SYMPTOM SCORE (IPSS) ........................60
APPENDIX 2.
ADAPTIVE DOSING CRITERIA ....................................................................61
APPENDIX 3.
HYPOGONADAL QUALITY OF LIFE (QOL) QUESTIONNAIRES ............65


TesoRx Pharma, LLC 
TSX-011 Dose Response Study
Protocol Number: TT-018
Confidential 
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1.
PROTOCOL SYNOPSIS
Title
A Phase 1/2a Study to Determine the Dose Response Pharmacokinetics of 
TSX-011 (Testosterone Undecanoate) in Hypogonadal Males
Sponsor 
TesoRx Pharma, LLC.
Investigational 
Product
TSX-011 for oral administration
Study Phase
Phase 1/2a
Study Number
TT-018
Study Objectives
The primary objective of the study is as follows:
1.
To assess the pharmacokinetics (PK) of total testosterone after oral 
dosing of TSX-011 in hypogonadal adult male subjects following: 
1) single ascending doses, and 2) single or multiple daily doses 
administered over a 30-day period in a fixed-dose and 
dose-adjustment adaptive design.
The secondary objectives of the study are as follows:
1.
To assess the safety and tolerability of TSX-011 in hypogonadal
adult male subjects by evaluating treatment-emergent adverse 
events (TEAEs).
2.
To assess the PK of free testosterone, testosterone undecanoate 
(TU), dihydrotestosterone (DHT), and dihydrotestosterone 
undecanoate (DHTU) after oral dosing of TSX-011 in hypogonadal 
adult male subjects following: 1) single ascending doses, and 
2) single or multiple daily doses administered over a 30-day period
in a fixed-dose and dose-adjustment adaptive design.
The exploratory objectives of the study are as follows: 
1.
To assess the effect of TSX-011 on hypogonadal symptoms as 
measured by hypogonadal quality of life (QOL) questionnaires:
Aging Male Symptom (AMS) scale, Multinational Survey of the 
Aging Male-7 (MSAM-7; libido questions only), and Psychosexual 
Daily Questionnaire (PDQ).
2.
To determine the preferred method of PK specimen collection
Serum or enzyme inhibited plasma.
Study Endpoints
The primary endpoints of the study are PK parameters for testosterone after
TSX-011 administration as described below.
1.
Period 1 (ascending single doses)
a.
Total (actual measured) testosterone: AUCt , Cmax, Tmax, 
Cmin, Tmin, and Cmax to Cmin ratio
b.
Baseline-corrected testosterone: z, t½, CL/F, Vss/F, 
AUClast, and AUC0 ∞


TesoRx Pharma, LLC 
TSX-011 Dose Response Study
Protocol Number: TT-018
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Page 8
2.
Period 2 (twice daily dosing) Day 1 and 15 and Period 3 Day 30 
(dose adjustment adaptive design)
a.
Total testosterone: AUCt, Css,avg, Cmax, Tmax, Cmin, Tmin, and 
Cmax to Cmin ratio
The secondary endpoints of the study are as follows:
1.
Number and severity of TEAEs and results of physical 
examinations, electrocardiograms (ECGs), vital sign measurements, 
and clinical laboratory tests (serum chemistry, hematology, and 
urinalysis) following a single dose of TSX-011 and following a 
single- or multiple-daily dose regimen of TSX-011 using a 
fixed-dose or a dose-adjustment adaptive design.
2.
PK parameters (AUC, Cmax, Cmin, Cavg, Tmax, Tmin) for free 
testosterone, TU, DHT, and DHTU under fed (or fasted) conditions 
following 1) ascending single doses of TSX-011, and 2) single- or 
multiple-daily dose regimen of TSX-011 (1 to 3 doses per day)
using a fixed-dose or dose-adjustment adaptive design.
The exploratory endpoints of the study are as follows:
1.
Hypogonadal symptoms as measured by hypogonadal QOL 
questionnaires: AMS, MSAM-7 (libido questions only), and PDQ.
2.
Duplicate PK analysis (serum and enzyme inhibited plasma) in the 
first 9 subjects enrolled.
Study Design
The study will be conducted as an open-label 3-period investigation as 
follows: 
Period 1. Ascending single-dose period: 190 mg TSX-011 (fed and 
fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed).
Period 2. 380 mg TSX-011 twice daily dosing period of 15 days in fed 
conditions.
Period 3. Dose-adjusted adaptive design period: TSX-011 dose 
adjustment permitted on Day 16 and Day 26 based on 6 hours 
postdose (± 15 minutes) testosterone level on Day 8 and Day 19, 
respectively; dosing period of 15 days.
Dosing amounts of TSX-011 in this protocol refer to TU amounts.  
Number of 
Subjects
Up to 24 subjects will be enrolled in this study to yield 16 evaluable 
subjects, and it is desired that the same 24 subjects participate in all 3 study 
periods.
The three initial cohorts of 3 subjects each will complete Periods 1, 2, and 3
prior to enrolment of remaining subjects.  Interim review of safety and 
efficacy of TSX-011 will occur prior to enrolment of remaining subjects in 
the study. Dose response and optimum dosing conditions and PK specimen 
collection methods (serum vs. enzyme inhibited plasma) will be confirmed 
prior to remaining subject enrolment. 


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Enrolment will be managed to result in at least 10 evaluable native Japanese 
subjects.  Subjects may be replaced at the discretion of the Sponsor in 
consultation with the Principal Investigator (PI).
Diagnosis and 
Inclusion Criteria
Inclusion Criteria 
Subjects will be eligible for the study if they meet the following criteria.
1.
Men 18 to 75 years of age at time of study enrolment.
2.
Male subjects (at least 1 serum testosterone level <350 ng/dL, 
10 am [± 2 hour] sample).  Subjects with a testosterone level 
≥350 ng/dL and <400 ng/dL may meet this inclusion criterion with 
a second sample taken at least 1 week after initial sample. 
3.
Native Japanese subjects (goal of 10 enrolled) must be men born in 
Japan who have relocated to the United States (US) and continue to 
practice a predominantly Japanese lifestyle and diet.  Japanese men 
should be first generation in the US with both Japanese parents and 
grandparents.  
4.
Able to meet the requirements of the study; to give voluntary, 
written informed consent; and to adhere to dosing and visit 
schedules for all 3 periods. 
5.
Body mass index (BMI) <35.0 kg/m2 and weight ≥50 kg at 
screening. 
6.
All sexually active subjects of reproductive potential are required to 
be sexually abstinent or use a condom with spermicide when 
engaging in sexual activity throughout the duration of the study and 
for 90 days after the last dose of study drug.
7.
Adequate venous access on left or right arm to allow collection of a 
number of blood samples by venipuncture.
8.
Adequate hematologic, hepatic, and renal parameters, 
i.e., hemoglobin >12 g/dL, alkaline phosphatase <130 U/L, and 
creatinine <1.3 mg/dL.
9.
Agrees not to donate sperm throughout the study from the first dose 
of study drug to 90 days after the last dose of study drug.
Exclusion Criteria  
Subjects will be ineligible for the study if they meet any of the following 
criteria:
1.
History of clinically significant renal, hepatic, neurologic, 
hematologic, endocrine, oncologic, pulmonary, immunologic, 
psychiatric, or cardiovascular disease or any other condition that, in 
the opinion of the PI, could jeopardize the safety of the subject or 
impact the validity of the study results. 
2.
Significant gastrointestinal or malabsorption conditions 
(e.g., history of cholecystectomy, gastroparesis, inflammatory 
bowel disease, pancreatitis, celiac disease, sprue, dumping 
syndrome, bariatric surgery, short bowel syndrome, lactose 
intolerance [unless subject avoids dairy products]).  Also, previous 


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surgery or a medical condition that, in the judgment of the PI, may 
affect absorption, distribution, metabolism, or elimination of the 
drug product (e.g., bariatric Roux-en-Y). 
3.
Any man in whom testosterone therapy is contraindicated including 
the following:
a.
Known or suspected carcinoma (or history of carcinoma) of 
the prostate, clinically significant symptoms of benign 
prostatic hyperplasia, and/or clinically significant 
symptoms of lower urinary obstruction and International 
Prostate Symptom Score (IPSS) ≥19.  A clinically 
significant digital rectal examination of the prostate (such 
as irregularities or nodules palpated, or otherwise 
suspicious for carcinoma of the prostate) or clinically 
significant elevated serum prostate-specific antigen (PSA)
levels (>4.0 ng/mL).  
b.
Known or suspected carcinoma (or history of carcinoma) of 
the breast.
c.
Liver disease defined as alanine aminotransferase (ALT) or 
aspartate aminotransferase (AST) >2 × upper limit of 
normal (ULN) or bilirubin >2 × ULN.
d.
Active deep vein thrombosis or thromboembolic disorder, 
or a documented history of these conditions.
e.
Untreated sleep apnea.
f.
Hematocrit >50%.
g.
Untreated moderate to severe depression.
4.
Current use of long-acting testosterone or any of the testosterone 
esters injectables. 
5.
Topical, oral, or injectable testosterone replacement therapy (any 
kind including dehydroepiandrosterone [DHEA] and nutritional 
supplements) within 28 days prior to screening; subjects who have 
used Testopel are excluded if it was used within the past 2 years, 
and subjects who have used AVEED are excluded if it was used 
within the past 6 months.
6.
Clinically significant changes in any medications (including 
dosages) or medical conditions in the 28 days before screening.
7.
Any significant history of allergy and/or sensitivity to the drug 
product or its excipients, including any history of sensitivity to 
testosterone or testosterone esters.
8.
Suspected reversible hypogonadism (e.g., leuprolide injection).
9.
Is taking concomitant medications that affect testosterone 
concentrations or metabolism (e.g., gonadotropin-releasing 
hormone [GnRH], 5α-reductase corticosteroids, or estradiol; see 
Section 9.1.2)


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10. Uncontrolled diabetes (screening glycated hemoglobin [HbA1c]
≥9%).
11. Any contraindication to blood sampling.
12. Intent to have any surgical procedure during the study.
13. Taken any investigational product as part of a clinical study within 
30 days or 5 half-lives of first administration of the investigational 
product, whichever is longer.
14. Donated blood or blood products or experienced significant blood 
loss within 90 days before dosing.
15. Donated bone marrow within 6 months before dosing.
16. History of drug or alcohol abuse in the last 6 months or positive 
result in urine drug screen.
17. Ingested St John’s wort within 30 days of screening.
18. Subject currently or planning to be on a special low-fat diet during 
the study.
19. Clinically significant positive result in virology tests (HIV, 
hepatitis). 
Study Duration
The approximate duration of participation for each subject in each study 
period is as follows:

Period 1: One day for each dose, plus a minimum 3-day and 
maximum 7-day washout between each single dose, yielding 9 to 
21 days from first single dose to last.

Periods 2 and 3: No less than a 3-day washout (no more than 
7 days [14 days for the three initial 3 subject cohorts]) following 
Period 1, followed by 2 consecutive 15-day dosing periods, yielding 
33 to 37 days (44 days for initial 3 subject cohorts). 
The study duration (after enrolment) for each subject will be approximately 
8 weeks. 
Treatments
In Period 1, 24 subjects will each receive single oral doses of 190, 380, and 
570 mg (TU) TSX-011 (8 am ± 60 minutes) under fed conditions in a 
sequential dosing, open-label study design.  In addition, the 190 mg TU 
dose will also be administered under fasted conditions as the second of the 
single doses administered in Period 1. The subjects will be given each of 
the 4 doses following a minimum 3-day washout from the previous dose.
In Period 2, after no less than a 3-day and no more than a 7-day washout
(14 days for initial 3 subject cohorts), the same 24 subjects will receive 
380 mg (TU) TSX-011 twice daily (8 am ± 60 minutes and 10 hours after 
morning dose) under fed conditions for 15 days.
In Period 3, the same 24 subjects will receive an adjusted dose of TSX-011 
(Appendix 2) under fed conditions for 15 days.  The first dose adjustment 
will be based on the 6 hours postdose (± 15 minutes) total testosterone on 
Day 8 during Period 2, and the second dose adjustment will be based on the 


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6 hours postdose (± 15 minutes) total testosterone on Day 19 during 
Period 3.
Analysis 
Populations
The analysis populations are defined as follows:
The Safety population is defined as all randomized subjects who received at 
least 1 dose of study drug and have at least 1 post-baseline safety 
assessment.
The PK population is defined as all enrolled subjects for whom at least 
one PK parameter of interest can be calculated.  In general, on a parameter 
by parameter basis, an individual subject’s data may be excluded from 
analysis if insufficient data are available for that subject to calculate the 
specific parameter in question.
The clinical batch population is defined as all enrolled subjects for whom at 
least one PK parameter of interest can be calculated.  This population will 
be stratified by dosed clinical study drug batch (e.g. first, second batch).  
Safety 
Assessments and 
Analysis
Adverse events (AEs), clinical laboratory test results, concomitant 
medications, vital signs, ECGs, and physical examinations. 
Pharmacokinetic 
Sample 
Collection and 
Analysis
Period 1: Blood samples for the determination of endogenous free 
testosterone, total testosterone, and DHT will be collected for a single 
24-hour period before any study subject exposure to TSX-011. This 
baseline assessment of endogenous androgen production will be assessed 
over a 24-hour predose interval (Day -1) at hour 0 (8 am ± 60 minutes) and 
post initial sample intervals of 1.5, 3, 4.5, 6, 8, 12, 16, and 24 hours (Day 1 
hour 0 sample). The initial cohort of 3 subjects will have duplicate PK 
samples (one serum and one plasma) taken prior to each dose and at each 
postdose collection point following all 4 doses per the instructions in the lab 
manual.  One of the duplicate samples will be serum and the other will be 
enzyme-inhibited plasma.
Blood samples for PK will be collected predose (hour 0) and for 24 hours 
postdose (1.5, 3, 4.5, 6, 8, 12, 16, and 24 hours) on Day 1 of each dose in 
Period 1 (190 mg TU fed, 190 mg TU fasted, 380 TU fed, and 570 mg TU
fed).
In addition, the second and third cohorts of 3 subjects each will have 
duplicate PK samples taken prior to the 570 mg TU dose and postdose 
collection points. The serum sample shall be processed initially, and only if 
TU is detectable at a level 5 times above the LLOQ (i.e. 10 ng/ml) shall the 
enzyme inhibited plasma sample undergo PK analysis.
Period 2: Blood samples for determination of free testosterone, total 
testosterone, TU, DHT, and DHTU will be collected at 8 am (± 60 minutes) 
and postdose intervals of 0, 1.5, 3, 4.5, 6, 8, 10, 11.5, 13, 14.5, 16, 18, and 
24 hours. In Period 2, a trough PK sample will be obtained before dosing 
on Day 8.
The initial three cohorts of 3 subjects each will have additional PK samples 
taken. Specifically, duplicate PK samples (one serum and one plasma) will 
be taken on Day 8 prior to dosing and at 6 hours (± 15 minutes) after the 


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morning dose.  The plasma sample values will be used to dose titrate 
according to the adaptive dosing design (Appendix 2).
For the first cohort, if TU is detectable at a level 5 times above the LLOQ 
(i.e. 10 ng/ml) in the previously collected Day 8 samples, then for PK 
assessments on Day 15, all blood samples will be collected in duplicate (one 
serum and one plasma).  
For the second and third cohorts, Day 15 samples will be collected in 
duplicate.  The serum sample shall be processed initially, and only if TU is 
detectable at a level 5 times above the LLOQ (i.e. 10 ng/ml) shall the 
enzyme inhibited plasma sample undergo PK analysis.
Period 3: For subjects on a once-daily dosing schedule, blood samples for 
determination of free testosterone, total testosterone, TU, DHT, and DHTU 
will be collected at 8 am (± 60 minutes) and postdose intervals of 0, 1.5, 3, 
4.5, 6, 8, 12, 16, and 24 hours.
For subjects on a twice-daily dosing schedule, blood samples for 
determination of free testosterone, total testosterone, TU, DHT, and DHTU
will be collected at 8 am (± 60 minutes) and postdose intervals of 0, 1.5, 3, 
4.5, 6, 8, 10, 11.5, 13, 14.5, 16, 18, and 24 hours.
Non-responder subjects (Cavg testosterone <350 ng/dL) after 1 dose 
adjustment (Day 16) will receive TSX-011 three times (thrice) daily.  For 
these subjects on the thrice-daily dosing schedule, blood samples for 
determination of free testosterone, total testosterone, TU, DHT, and DHTU
will be collected at 8 am (± 60 minutes) and postdose intervals of 0, 1.5, 3, 
4.5, 6, 8, 9.5, 11, 12.5, 14, 15.5, 17, 18.5, 20, and 24 hours.
The three initial cohorts of 3 subjects each will have additional PK samples 
taken. Specifically, duplicate PK samples (one serum and one plasma) will 
be taken on Day 19 prior to dosing and at 6 hours (± 15 minutes) after the 
morning dose.  The plasma sample values will be used to dose titrate 
according to the adaptive dosing design (Appendix 2).
For the first cohort, if TU is detectable at a level 5 times above the LLOQ 
(i.e. 10 ng/ml) in the previously collected Day 19 samples, then for PK 
assessments on Day 30, all blood samples will be collected in duplicate (one 
serum and one plasma).  
For the second and third cohorts, Day 30 samples will be collected in 
duplicate.  The serum sample shall be processed initially, and only if TU is 
detectable at a level 5 times above the LLOQ (i.e. 10 ng/ml) shall the 
enzyme inhibited plasma sample undergo PK analysis.
Pharmacokinetic
Statistics
Details of the PK data analysis are specified in the statistical analysis plan.  
PK parameters for free testosterone, total testosterone, TU, DHT, and 
DHTU given under fed (or fasted) condition after TSX-011 dosing will be 
determined at all periods of the study. TSX-011 responders are defined as 
study subjects who are able to achieve a Cmax testosterone > 350 ng/dL
within Period 1 and Cavg testosterone > 350 ng/dL in Period 2 and 3.  For 
this protocol, Cmax testosterone is defined as the testosterone level obtained 
6 hours postdose (± 15 minutes) on days designated for dose adjustment. 
The following PK parameters will be calculated:


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1) Period 1, ascending single doses of TSX-011: Total testosterone, AUCt, 
Cmax, Tmax, Cmin, Tmin, and Cmax to Cmin ratio. Baseline-corrected
testosterone: z, t½, CL/F, Vss/F, Cmax, AUClast, and AUC∞.
2) Period 2 and 3: Days 1, 15, and 30 total testosterone given as once, 
twice, or thrice daily dosing of TSX-011 provided in a dose-adjustment 
adaptive design: AUCt, Css,avg, Cmax, Tmax, Cmin, Tmin, and the Cmax to Cmin
ratio.
PK parameters for free testosterone, TU, DHT, and DHTU following: 1) 
ascending single doses, and 2) a once, twice, or thrice daily dose adjustment 
adaptive design of TSX-011: AUCt, Cmax, Cmin, Tmax, Cssavg, and Tmin.
To assess dose proportionality, analysis of variance will be performed on 
the ln-transformed PK parameters: AUCs and Cmax.
Dose response will be evaluated via a linear mixed model with random 
subject effect to account for multiple-dose levels per subject.
TSX-011 non-responders are defined as study subjects who despite dose 
adjustments (in Periods 2 and 3) are unable to achieve a Cavg testosterone > 
350 ng/dL.
Interim review of safety and efficacy of TSX-011 for the three initial 3 
subject cohorts will occur prior to enrolment of remaining subjects in the 
study. Protocol amendments may be generated after these initial 3-patient 
cohorts.
Safety Statistics
Safety data including laboratory evaluations, physical examinations, AEs, 
standard 12-lead ECG parameters, and vital signs assessments will be 
summarized by treatment group and time point of collection, when 
appropriate. 
Adverse events will be coded using the most recent version of the Medical 
Dictionary for Regulatory Activities (MedDRA®). A by-patient AE listing 
by MedDRA system organ class and by preferred term within system organ 
class, including verbatim term, dose level, severity, and relationship to 
treatment, will be provided. This listing will include all AEs and serious 
AEs (SAEs).
Descriptive statistics (arithmetic mean, standard deviation [SD], coefficient 
of variation [CV], median, minimum, and maximum) will be calculated for 
quantitative safety data as well as for the difference from baseline, when 
appropriate.
Tables summarizing shifts in clinical laboratory results with respect to 
normal range will be provided, as well as tables summarizing shifts in vital 
signs and standard 12-lead ECGs with respect to normal and abnormal 
results.
Concomitant medications will be listed by treatment and coded using the 
most recent version of the World Health Organization Drug Dictionary. 
Bioanalytical 
Method
See laboratory manual for details.


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2.
SCHEDULE OF EVENTS
Table 1:
Schedule of Events - Period 1: Ascending Single Doses
Event
Screening
(Day -30 
to -1)
Single Treatment Doses1 of 1902, 380, and 570 mg TU TSX-011 
(8 am ± 60 minutes)
Screen
Day -2
Day -1
Day 1
Day 2
(+4 days)
Post Dose (hours)
0
1.5
3
4.5
6
8
12
16
24
Confinement
Confined in Study Unit
Inclusion/exclusion
■
■
Informed consent
■
Medical history3
■
ECG (12 lead)
■
■
■
Vital signs4,5
■
■
■
■
■
Weight/height/BMI
■
Physical examination4
■
■
■
HbA1c test
■
Testosterone levels
■
■6
Virology tests
■
Chemistry/hematology
■
■
■
Urinalysis
■
■
■
PSA
■
Urine drug\alcohol screen
■
■
IPSS, QOL questionnaires
■
Drug administration
■


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PK sampling7
■8
■
■
■
■
■
■
■
■
■
Adverse events
Continual AE monitoring throughout the study duration9
Continual concomitant medication monitoring throughout the study
Concomitant medications
AE = adverse event; BMI = body mass index; ECG = electrocardiogram; HbA1c = glycated hemoglobin; IPSS = International Prostate Symptom Score; 
PK = pharmacokinetic(s); PSA = prostate-specific antigen; QOL = quality of life
1 There will be a washout period of at least 3 days and up to 7 days between each dose.
2 190 mg dose to be provided in both the fed and fasted state.
3 Demographic information will also be collected. 
4 These safety assessments can also be performed at any time at the discretion of the Principal Investigator.
5 Sitting (5 minutes) blood pressure, pulse rate, respiration rate, and temperature; repeat blood pressure 5 minutes later if elevated.
6 Testosterone levels (local lab) needed after each ascending dose; dose escalation permitted if testosterone is < 2500 ng/dL.
7 Three initial cohorts of 3 subjects each will have duplicate PK samples (one serum and the other plasma) taken per the descriptions in Section 11.1.
8 Endogenous baseline testosterone production will be measured before exposure to TSX-011 in Period 1 (per the instruction in the lab manual).  With subject 
confined in study center, a 24-hour blood sample will be obtained at the following time points: hour 0 (8 am ± 60 mins), and 1.5, 3, 4.5, 6, 8, 12, 16, and 24
hours (± 15 minutes for each time point). The last sample can also be used as the Day 1 hour 0 sample. 
9 Details on study monitoring of AEs are presented in Section 10.5.2.


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Table 2:
Schedule of Events - Period 2: 380 mg bid, Starting 3-7 Days After Last Dose of Period 1 
Event
Twice Daily 380 mg TSX-011 Dosing (8 am± 60 min and 10 hrs post morning dose ± 15 min)
Day -1
Day 1
Day 2
Day 8
Post Dose (hours)
0
1.5
3
4.5
6
8
10
11.5
13
14.5
16
18
24
Confinement
Confined in Study Unit
Vital signs
■
■
■
■
■
■
Physical examination
■
ECG (12 lead)
■
■
Testosterone levels
■2
Chemistry/hematology
■
■
Urinalysis
■
■
Urine drug/alcohol screen
■
IPSS, QOL questionnaire
■
Drug administration
■
■
■
■
PK sampling
■
■
■
■
■
■
■
■
■
■
■
■
■
■2,3
Adverse events
Continual AE monitoring throughout the study duration4
Continual concomitant medication monitoring throughout the study duration
Concomitant meds
AE = adverse event; bid = twice daily; Cmax = maximum serum concentration; IPSS = International Prostate Symptom Score; meds = medications; 
min = minutes; PK = pharmacokinetic(s); QOL = quality of life
1 There will be a washout period of at least 3 days and up to 7 days (14 days for the three initial 3 subject cohorts) between Period 1 and Period 2. 
2 Testosterone levels 6 hours postdose (± 15 minutes) on Day 8 will be used to select TSX-011 dose on Period 3, Day 16 per Appendix 2.   
3 Day 8 trough PK sample before 8 am dose administration. 
4 Details on study monitoring of AEs are presented in Section 10.5.2.


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Table 3:
Schedule of Events - Period 2 (continued): 380 mg bid, Starting 3-7 Days After Last Dose of Period 1
Event
Twice Daily 380 mg TSX-011 Dosing (8 am ± 60 min and 10 hrs post morning dose ± 15 min)
Day 14
Day 15
Day 161
Post Dose (hours)
0
1.5
3
4.5
6
8
10
11.5
13
14.5
16
18
24
Confinement
Confined in Study Unit
ECG (12 lead)
■
Vital signs
■
■
■
■
■
Physical examination
■
■
Chemistry/hematology
■
Urinalysis
■
Urine drug/alcohol screen
■
IPSS, QOL questionnaires
■
Drug administration
■
■
■
■
Dose adjustment
■
PK sampling2
■
■
■
■
■
■
■
■
■
■
■
■
■
Adverse events
Continual AE monitoring throughout the study duration3
Continual concomitant medication monitoring throughout the study duration
Concomitant meds
AE = adverse event; bid = twice daily; ECG = electrocardiogram; IPSS = International Prostate Symptom Score; meds = medications; min = minutes; PK = pharmacokinetic(s); QOL = quality of life
1 This is the first day of Period 3.
2 On Day 15, duplicate PK samples will be obtained for subjects in Cohorts 2 and 3 (see Section 11.1 for criteria).
3 Details on study monitoring of AEs are presented in Section 10.5.2.


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Table 4:
Schedule of Events - Period 3: Adaptive Dose Phase for Once-daily Dosing
Event
Once-daily TSX-011 Dosing (8 am ± 60 minutes)
Day 191
Day 26
Day 29
Day 30
Day 31 (exit)
Post Dose (hours)
0
1.5
3
4.5
6
8
12
16
24
Confinement
Confined to Study Unit
ECG (12 lead)
■
Vital signs
■
■
Physical examination
■
■
Testosterone levels
■2
Chemistry / hematology
■
Urinalysis
■
PSA
■
Urine drug/alcohol screen
■
IPSS, QOL questionnaires
■
■
Drug administration
■
■
■
■
Dose adjustment
■1
PK sampling2
■1
■
■
■
■
■
■
■
■
■
Adverse events
Continual AE monitoring throughout the study duration3
Continual concomitant medication monitoring throughout the study duration
Concomitant meds
AE = adverse event; ECG = electrocardiogram; IPSS = International Prostate Symptom Score; meds = medications; PK = pharmacokinetic(s); PSA = prostate specific antigen; QOL = quality of life
1 Testosterone levels 6 hours postdose (± 15 minutes) on Day 19 will be used to select TSX-011 dose on Day 26 per the rules outlined in Appendix 2.
2 On Day 30, duplicate PK samples will be obtained for subjects in Cohorts 2 and 3 (see Section 11.1 for criteria).
3 Details on study monitoring of AEs are presented in Section 10.5.2.


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Table 5:
Schedule of Events - Period 3: Adaptive Dose Phase for Twice-daily Dosing
Event
Twice-daily TSX-011 Dosing (8 am ± 60 minutes and 10 hrs post morning dose ± 15 minutes)
Day 191
Day 26
Day 29
Day 30
Day 31 (exit)
Post Dose (hours)
0
1.5
3
4.5
6
8
10
11.5
13
14.5
16
18
24
Confinement
Confined to Study Unit
ECG (12 lead)
■
Vital signs
■
■
Physical examination
■
■
Testosterone levels
■1
Chemistry / hematology
■
Urinalysis
■
PSA
■
Urine drug/alcohol screen
■
IPSS, QOL questionnaire
■
■
Drug administration
■
■
■
■
■
Dose adjustment
■1
PK sampling2
■1
■
■
■
■
■
■
■
■
■
■
■
■
■
Adverse events
Continual AE monitoring throughout the study duration3
Continual concomitant medication monitoring throughout the study duration
Concomitant medications
AE = adverse event; ECG = electrocardiogram; IPSS = International Prostate Symptom Score; PK = pharmacokinetic(s); PSA = prostate specific antigen; QOL = quality of life
1 Testosterone levels 6 hours postdose (± 15 minutes) on Day 19 will be used to select TSX-011 dose on Day 26 per the rules outlined in Appendix 2.
2 On Day 30, duplicate PK samples will be obtained for subjects in Cohorts 2 and 3 (see Section 11.1 for criteria).
3 Details on study monitoring of AEs are presented in Section 10.5.2.


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Table 6:
Schedule of Events - Period 3, Adaptive Dose Phase for Thrice-daily Dosing
Event
Thrice-daily TSX-011 Dosing
(8 am± 60 mins, 8 hrs post morning dose ± 15 mins, and 14 hrs post morning dose ± 15 mins)
Day 191
Day 26
Day 29
Day 30
Day 31 (exit)
Post Dose (hours)
0
1.5
3
4.5
6
8
9.5
11
12.5
14
15.5
17
18.5
20
24
Confinement
Confined to Study Unit
ECG (12 lead)
■
Vital signs
■
■
Physical examination
■
■
Testosterone levels
■1
Chemistry / hematology
■
Urinalysis
■
PSA
■
Urine drug\alcohol screen
■
IPSS, QOL questionnaire
■
■
Drug administration
■
■
■
■
■
■
Dose adjustment
■1
PK sampling2
■1
■
■
■
■
■
■
■
■
■
■
■
■
■
■
■
Adverse events
Continual AE monitoring throughout the study duration3
Continual concomitant medication monitoring throughout the study duration
Concomitant medications
AE = adverse event; ECG = electrocardiogram; IPSS = International Prostate Symptom Score; mins = minutes; PK = pharmacokinetic(s); PSA = prostate specific antigen; QOL = quality of life
1 Testosterone levels 6 hours postdose (± 15 minutes) on Day 19 will be used to select TSX-011 dose on Day 26 per the rules outlined in Appendix 2.
2 On Day 30, duplicate PK samples will be obtained for subjects in Cohorts 2 and 3 (see Section 11.1 for criteria).
3 Details on study monitoring of AEs are presented in Section 10.5.2.


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3.
LIST OF ABBREVIATIONS
ADL
Activities of daily living
ADR
Adverse drug reaction
AE
Adverse event
ALT
L-alanine aminotransferase
AST
L-aspartate aminotransferase
AUC
Area under the curve
AUClast
Area under the concentration versus time curve from time 0 to the last 
measurable concentration
AUCt
Area under the concentration versus time curve, from time 0 to the last 
measurable concentration on or before time t
AUC∞
Area under the concentration versus time curve from time 0 to infinity
BC
Baseline corrected 
BMI
Body mass index
BUN
Blood urea nitrogen
Cavg,ss
Steady-state average drug concentration
CFR
Code of Federal Regulations
CI
Confidence interval
CL/F
Apparent total body clearance after oral dosing
Cmax
Maximum drug concentration
Cmin
Minimum drug concentration
CV
Coefficient of variation
CYP
Cytochrome P450
DHT
Dihydrotestosterone
DHTU
Dihydrotestosterone undecanoate
DSPC
Distearoylphosphatidylcholine
ECG
Electrocardiogram 
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GnRH
Gonadotropin-releasing hormone
HbA1c
Glycated hemoglobin
HIV
Human immunodeficiency virus
ICH
International Conference on Harmonisation
IPSS
International Prostate Symptom Score
MedDRA®
Medical Dictionary of Regulatory Activities®
NF
National Formulary
PDQ
Psychosexual Daily Questionnaire
PI
Principal Investigator


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PK
Pharmacokinetic(s)
PSA
Prostate specific-antigen
REC
Research ethics committee
SAE
Serious adverse event
SAP
Statistical analysis plan
SD
Standard deviation
SOP
Standard operating procedure
SUSAR
Suspect unexpected serious adverse reaction
TEAE
Treatment-emergent adverse event
Tmax
Time of the maximum measured concentration over the specified 
interval.  If the maximum value occurs at more than one time point, Tmax
is defined as the first time point with this value.
Tmin
Time of the minimum measured concentration over the specified interval
TU
Testosterone undecanoate
t1/2
Apparent elimination half-life
ULN
Upper limit of normal
US
United States
USP
United States Pharmacopeia
Vss/F
Volume of distribution at steady state after oral dosing
WHO
World Health Organization
z
Apparent elimination rate constant


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4.
INTRODUCTION
Native testosterone is not bioavailable after oral administration because of low aqueous 
solubility, presystemic enterocyte-based cytochrome P450 (CYP) metabolism, and 
extensive first-pass hepatic metabolism after absorption via the portal vein.  Commercial 
testosterone products address this problem by providing testosterone for parenteral routes 
of administration (e.g., transdermal patches or gels and intramuscular injections or 
implants), or by providing a chemical derivative of the testosterone molecule that hinders 
hepatic uptake and decreases the rate of hepatic metabolism.
Currently approved formulations have significant drawbacks, such as:
1. Testosterone injection and implants: inflammation and pain at the site of 
administration
2. Testosterone gels:  issues with secondary exposure and adverse events (AEs)
associated with supraphysiologic doses
3. Testosterone patches:  skin irritation and elevated dihydrotestosterone (DHT)
Several androgenic therapies employing testosterone and testosterone ester formulations 
have been developed to increase serum testosterone levels.  Oral testosterone 
undecanoate (TU) has been marketed for testosterone replacement therapy outside of the 
US for over 20 years as Andriol Testocaps®.  The Nebido® or Reandron® product 
(injectable TU) has recently become available in 36 countries.  Other esterified 
testosterone products have been approved for injection by the Food and Drug 
Administration (FDA), including testosterone cypionate, testosterone enanthate, and 
testosterone propionate.  
TesoRx Pharma, LLC (TesoRx) has developed a novel approach for the oral 
administration of testosterone based on TSX-011, a novel proliposomal formulation of 
TU that achieves significant oral bioavailability.  
After passing through the intestinal epithelium, TSX-011 is absorbed into the lymphatic 
system rather than into the capillaries of the portal system.  Thus, the testosterone derived
from TSX-011 enters the systemic circulation via the lymphatics instead of via the portal 
vein to the liver (Hirano and Hunt, 1985).  This allows the testosterone derived from 
TSX-011 to bypass presystemic hepatic metabolism, which can improve oral 
bioavailability of drugs that undergo extensive first-pass metabolism (Vorshosaz et al., 
2010).
The drug substance in TSX-011 is testosterone undecanoate United States Pharmacopeia 
(USP). Testosterone undecanoate (17β-undecanoyloxy-4-androsten-3-one) is an inactive
prodrug ester of the androgen testosterone that has very weak binding affinity for the 
androgen receptor. Testosterone is formed by nonspecific esterase cleavage of the ester 
side chain of TU.
For detailed information on TSX-011 and its excipients, refer to the Investigator’s
Brochure.
Dosing amounts of TSX-011 in this protocol refer to TU amounts.  


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4.1.
Pharmacologic Profile
TSX-011 is a novel proliposomal formulation of TU that achieves significant oral 
bioavailability by enhancing lymphatic uptake of the drug from the gastrointestinal tract, 
thereby limiting passage of the drug through the portal vein to the liver and, hence, 
hepatic metabolism of testosterone.
4.2.
Toxicology
The active ingredient in the TSX-011 formulation is testosterone undecanoate USP, for 
which decades of clinical and nonclinical experience exist.  Testosterone undecanoate is 
currently marketed in the United States (US) for the intramuscular route of administration 
at doses of up to 750 mg every 10 weeks (e.g., AVEED®, New Drug Application [NDA] 
#22-219).  According to the FDA review of the pharmacology and toxicology of
AVEED, the overall results of the nonclinical program were similar to what would be 
expected for testosterone.
Exogenous exposure to testosterone or testosterone esters has resulted in common 
adverse responses in men including:  elevated DHT and estradiol (metabolites of 
testosterone), reduced fertility, gynecomastia, behavioral changes, sleep apnea, edema 
(retention of sodium, chloride, potassium, and inorganic phosphates), increased prostatic 
hyperplasia, increased platelet aggregation and thrombogenicity, altered serum lipid 
profile, polycythemia, and liver and kidney toxicity.
4.3.
Pharmacokinetic Profile
The TSX-011 pharmacokinetic (PK) profile in humans is unknown; however, the 
TSX-011 PK profile in beagle dogs indicates a gradual, broad increase in plasma 
testosterone concentration, with dose proportionality observed over the dosing range 
3.75, 7.5, and 11.25 mg/kg, and no evidence of significant exposure difference following 
a regular-fat meal versus a high-fat meal.  Optimal dosing conditions in the beagle dog 
are in the fed condition.
The PK profile of the injectable AVEED formulation of TU is described in the AVEED
label.  AVEED delivers physiologic amounts of testosterone when administered in 
accordance with the prescribing information; circulating testosterone concentrations 
approximate normal concentrations in healthy men (approximately 300 to 1000 ng/dL).  
Following intramuscular injection of 750 mg of AVEED, serum testosterone
concentrations reach a maximum after a median of 7 days (range 4 to 42 days) and then 
slowly decline.  Steady-state serum testosterone concentration is achieved with the third 
injection of AVEED at 14 weeks.
AVEED is the only marketed formulation of TU in the US; no oral formulations are 
approved for use.  TSX-011 has been designed to provide dosing via oral administration.  
This study is designed to determine the daily oral dose of TSX-011 needed to achieve 
normal concentrations (300 to 1000 ng/dL) of testosterone in males with serum 
testosterone level <350 ng/dL.


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4.4.
Clinical Experience
No clinical trials have been conducted with TSX-011.  
TesoRx has conducted clinical studies with a similar proliposomal formulation of 
testosterone (TSX-002; IND 110712).  The composition of TSX-002 is almost identical 
to TSX-011; testosterone is replaced with TU to improve bioavailability, reduce venous 
uptake from the intestine and thereby decrease first-pass hepatic metabolism, and 
cholesterol has also been removed from the formulation.  In 3 studies, a total of 
171 subjects were treated with TSX-002.  One serious adverse event (rhabdomyolysis; 
deemed not related by the principal investigator [PI] and sponsor) and no serious adverse 
reactions occurred during the studies.  Although no clinical trials in humans have been 
completed with TSX-011, 2 oral non-GLP toxicology studies in dogs demonstrated that 
oral TSX-011 was well tolerated for up to 7 days of continuous twice daily dosing.  
TesoRx believes that TSX-011 will have a similar safety profile to TSX-002.  
4.5.
Study Rationale
The rationale for this study is to determine the feasibility of oral testosterone replacement 
therapy with proliposomal TSX-011. The premise of the TSX-011 development program 
is that delivering TU in a proliposomal formulation will enable a safer (e.g., less risk of 
hepatic events; more flexible dosing) and more convenient treatment for hypogonadism 
than is available with currently marketed testosterone formulations and modified 
testosterone products.


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5.
STUDY OBJECTIVES
5.1.
Study Objectives
The primary objective of the study is as follows:
1. To assess the PK of total testosterone after oral dosing of TSX-011 in 
hypogonadal adult male subjects following: 1) single ascending doses, and 
2) single or multiple daily doses administered over a 30-day period in a 
fixed-dose and dose-adjustment adaptive design.
The secondary objectives of the study are as follows:
1. To assess the safety and tolerability of TSX-011 in hypogonadal adult male 
subjects by evaluating treatment-emergent adverse events (TEAEs).
2. To assess the PK of free testosterone, TU, DHT, and DHTU after oral dosing of 
TSX-011 in hypogonadal adult male subjects following: 1) single ascending 
doses, and 2) single or multiple daily doses administered over a 30-day period in a
fixed-dose and dose-adjustment adaptive design.
The exploratory objectives of the study are as follows: 
1. To assess the effect of TSX-011 on hypogonadal symptoms as measured by 
hypogonadal quality of life (QOL) questionnaires: Aging Male Symptom (AMS)
scale, Multinational Survey of the Aging Male-7 (MSAM-7; libido questions
only), and the Psychosexual Daily Questionnaire (PDQ).
2.
To determine the preferred method of PK specimen collection
Serum or enzyme 
inhibited plasma.


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6.
INVESTIGATIONAL PLAN
6.1.
Overall Study Design
This will be a phase 1/2a, open-label, single-center study with 3 periods.  The aims of the 
study are to: 1) evaluate the dose-response curve following ascending single doses of 
TSX-011; 2) confirm optimum dosing conditions; 3) evaluate the efficacy of single or 
multiple daily adaptive dosing; and 4) evaluate the safety and tolerability of TSX-011. 
Up to 24 hypogonadal men will be enrolled in this study to yield 16 evaluable subjects, 
and it is desired that the same 24 subjects participate in all 3 study periods. A diagram of 
the study design is presented in Figure 1.  The schedule of events is presented in Table 1
(Period 1), Table 2 (Period 2 up to Day 8), Table 3 (Period 2 from Day 14 to Day 16), 
Table 4 (Period 3 for single-daily dosing), Table 5(Period 3 for twice-daily dosing), and
Table 6 (Period 3 for thrice-daily dosing).
Figure 1:
Study Design for Study TT-018
T = testosterone
n = 24
Single dose escalation
Each dose (190(fed/fasted), 380
and 570 mg TU) administered once
to each patient
Period1
3-7day washout (3-14dayfor three initial3
subject cohorts) between Period1andPeriod2
Stable dose: 15 Days
15 days on 380 mg TU dose
(twice daily)
Period 2
No washout between Period2and
Period3
Dose titration: Day 16-
30 (once, twice, or thrice daily)
Dose adjustment on days 16 and
Period 3
26.
Day 16 dose adjustment based on
6 hours post-dose Day 8 T-level
Day 26 dose adjustment based on
6 hours post-dose Day 19 T-level.


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Period 1 (Figure 1 and Table 1) is an ascending single-dose study of TSX-011 at 3 doses, 
with the lowest dose administered under fed and fasted conditions:  190 mg TSX-011 in 
the fed state, 190 mg TSX-011 in the fasted state, 380 mg TSX-011 in the fed state, and 
570 mg TSX-011in the fed state. Before exposure to TSX-011, a 24-hour baseline 
measurement of testosterone and DHT will be performed for each subject.  Samples for 
analysis of testosterone will be obtained at the following time points on Day -1:  hour 0 
(8 am ± 60 minutes) and 1.5, 3, 4.5, 6, 8, 12, 16, and 24 hours (± 15 minutes for each 
time point).
The day following the sampling for endogenous testosterone (Day 1) in Period 1, each 
subject will receive the first single dose of TSX-011 (190 mg) under fed conditions.
Following administration of TSX-011, blood samples will be obtained over a 24-hour 
period for PK analysis.  Subjects will undergo a minimum 3-day and up to 7-day washout 
period between each of the doses of TSX-011 in Period 1.  After the 570 mg TSX-011 
dose in Period 1, a minimum 3-day and up to 7-day (14 day for three initial 3 subject 
cohorts) washout period will occur before the start of Period 2.
Period 2 is a twice-daily dosing period (Figure 1, Table 2, and Table 3), where fed
subjects will be dosed with 380 mg TSX-011 twice daily (at 8 am and 6 pm
± 60 minutes) for 15 days (Days 1 through 15). Pharmacokinetic assessments over 
24 hours will occur on Days 1 and 15.  On Day 8 in Period 2, before the morning dose, a 
trough PK blood sample will be drawn. In addition, on Day 8, 6 hours (± 15 minutes)
after the morning dose, testosterone levels will be obtained and used to dose titrate 
according to the adaptive dosing design (Appendix 2). The TSX-011 dose will be titrated
up or down beginning with the Day 16 (Period 3) morning dose, based on established
dosing rules (see Appendix 2).
Period 3 is a dose-adjusted adaptive design period that begins on Day 16, with the first 
adjusted TSX-011 dose (see Appendix 2 and randomization scheme) administered in the 
fed state on a once-daily or twice-daily schedule. The 6-hour postdose (± 15 minutes)
testosterone level on Day 19 will be used to perform the second and final TSX-011 dose 
adjustment, based on established criteria. As specified by the dose adjustment rules in 
Appendix 2, Day 26 begins with either a once-daily, twice-daily, or thrice-daily fed dose 
schedule (Table 4, Table 5, and Table 6, respectively).  The thrice-daily dose schedule 
will be administered only to non-responders (Cavg testosterone <350 ng/dL despite 1 dose 
adjustment).  On Day 30, a 24-hour PK assessment will be performed, and the subject’s 
participation in the study is completed the morning of Day 31.
Three starting cohorts of 3 subjects each will complete Periods 1, 2, and 3 prior to 
enrolment of the remaining subjects (see Figure 2).  For purpose of this protocol 
‘enrolment’ is the subject first dose (i.e., 190 mg fed Day 1).  An interim review of TSX-
011 safety and efficacy data (including PK data) will occur prior to enrolling the 
remaining subjects in the study. Any subject in these cohorts who fails to complete all 3
study periods or is determined to be a non-responder will be replaced. For the first 
cohort, duplicate PK samples (one serum and one plasma) will be taken prior to each 
dose and at each postdose collection point following all 4 period 1 doses and analyzed 
per instruction in the lab manual. One of the duplicate samples will be serum and the 


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other will be enzyme-inhibited plasma. Additional duplicate samples will be collected 
per the descriptions in Section 11.1. 
Figure 2:
Study Cohort Enrolment Design
6.2.
Study Endpoints
The primary endpoints of the study are PK parameters for testosterone after TSX-011 
administration under fed (or fasted [Period 1, 190 mg dose only]) conditions as described 
below:
1. Period 1 (ascending single doses): 
a.
Total (actual measured) testosterone, AUCt, Cmax, Tmax, Cmin, Tmin, and 
Cmax to Cmin ratio.
b. Baseline-corrected (BC) testosterone: z, t½, CL/F, Vss/F, Cmax, AUClast,
and AUC∞.
2. Period 2 (twice-daily dosing) Days 1 and 15 and Period 3 (dose-adjustment 
adaptive design) Day 30:
a.
Total testosterone: AUCt, Css,avg, Cmax, Tmax, Cmin, Tmin, and Cmax to Cmin
ratio.
The secondary endpoints of the study are as follows:
1. Number and severity of TEAEs and results of physical examinations, 
electrocardiograms (ECGs), vital sign measurements, and clinical laboratory tests
(serum chemistry, hematology, and urinalysis) following a single dose of 
TSX-011 and following a single- or multiple-daily dose regimen of TSX-011 
using a fixed-dose or a dose-adjustment adaptive design.
n
Three Initial
Cohorts
complete all
3 periods
Enroll remaining
subjects
Interim
Reviews
Protocol Adjustment of
Adaptive Dosing Criteria


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2. PK parameters (AUCt, Cmax, Tmax, Cmin, and Cavg) for free testosterone, TU, DHT, 
and DHTU under fed (or fasted [Period 1, 190 mg dose only]) conditions 
following: 1) ascending single doses of TSX-011, and 2) single- or multiple-daily 
dose regimen of TSX-011 using a fixed-dose and dose-adjustment adaptive 
design. 
The exploratory endpoints of the study are as follows:
1. Hypogonadal symptoms as measured by the hypogonadal QOL questionnaires: 
AMS scale, MSAM-7 (libido questions only), and PDQ.
2.
Duplicate PK analysis (serum and enzyme inhibited plasma) in the first 9 subjects 
enrolled.
6.3.
Treatments
Period 1:
Eligible subjects will receive ascending doses of TSX-011 at 8 am (± 60 minutes) in the 
following order: 190 mg fed, 190 mg fasted, 380 mg fed, and 570 mg fed.  The second
dose will follow an overnight fast of at least 6 hours duration, and food will be given 
2 hours after dosing.  Fed doses will be followed by a breakfast 15 minutes
(± 15 minutes) after dosing.  A minimum 3-day and up to 7-day washout will occur 
between doses.  Up to 24 subjects will be tested, to yield at least 16 evaluable subjects.
Period 2:
Subjects in a fed state will receive 380 mg TSX-011 twice daily (8 am ± 60 minutes and 
10 hours ± 15 minutes post morning dose) for 15 days. Subjects will be permitted to eat 
breakfast and dinner 15 minutes (± 15 minutes) after the morning and evening doses, 
respectively. In addition, a snack will be permitted between 2 and 3 pm.  On Day 8, a 
predose blood sample for trough PK will be obtained.  On Day 8, 6 hours post dose
(± 15 minutes), a blood sample will be drawn for testosterone analysis, and the results 
will be used to determine dose adjustment for Period 3 (beginning on Day 16).
Period 3:
On Day 16, subjects will receive an adjusted dose of TSX-011 (see Appendix 2), fed
(8 am ± 60 minutes and 10 hours post morning dose ± 15 minutes).  The second TSX-011 
dose adjustment will be based on a blood sample for testosterone analysis obtained 
6 hours (± 15 minutes) after the morning dose on Day 19, and will start with the morning
dose on Day 26. The dose adjustment will be based on criteria specified in Appendix 2.  
Subjects will receive the adjusted dose of TSX-011 either once daily fed (8 am
± 60 minutes), twice daily fed (8 am ± 60 minutes and 10 hours post morning dose 
± 15 minutes), or, for non-responders only (Cavg testosterone <350 ng/dL after 1 dose 
adjustment), thrice daily fed (8 am ± 60 minutes, 8 hours post morning dose 
± 15 minutes, and 14 hours post morning dose ± 15 minutes) for the final 5 days of 
Period 3. 


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6.4.
Stopping Rules of Dose Escalation
Interim review of safety and PK data will be performed at the following times during the 
study:

On completion of Period 3 by the initial three cohorts of 3 subjects each.  
Interim reviews to be completed prior to enrolment of remaining subjects.
Informal safety reviews will be conducted in between the dose escalations of Period 1 
and Period 3. The informal reviews may include a safety meeting, but it is not required.
Dose escalation will be halted for a subject in the event of any of the following:

An incidence of a serious/severe adverse drug reaction (ADR) among subjects
that, in the opinion of the PI or the Sponsor, necessitates discontinuation of 
dose escalation.

An incidence of a treatment-related, clinically significant laboratory event
that, in the opinion of the PI or the Sponsor, necessitates discontinuation of 
dose escalation.

A serum testosterone Cmax exceeding 2500 ng/dL. Subjects experiencing 
testosterone levels >2500 ng/dL will be discontinued from further dose 
escalation treatment with TSX-011 and be followed until testosterone levels 
normalize or return to baseline; subject will be eligible to continue at TSX-
011 dose that did not result in supra-physiological Cmax values. 

If any subject develops a hemoglobin of 18 g/dL or higher, or a hematocrit of 
54% or higher, the drug should be discontinued.
Prior to each interim review, the following data will be reviewed by the Sponsor and/or 
Sponsor representative(s) and the PI: 

Vital signs assessments

ECG assessments

Safety laboratory analysis

AEs assessment

PK analysis
Study progression will be permitted only if adequate safety and tolerability have been 
demonstrated at the previous lower dose, as agreed by the PI and the Sponsor. 


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7.
SELECTION, EXCLUSION AND WITHDRAWAL 
CRITERIA
7.1.
Inclusion Criteria
Subjects will be eligible for the study if they meet the following criteria.
1. Men 18 to 75 years of age at time of study enrolment.
2. Male subjects (at least 1 serum testosterone level <350 ng/dL, 10 am [± 2 hour]
sample).  Subjects with testosterone level ≥350 ng/dL and <400 ng/dL may meet 
this inclusion criterion with a second sample taken at least 1 week after initial 
sample. 
3. Native Japanese subjects (goal of 10 enrolled) must be men born in Japan who 
have relocated to the US and continue to practice a predominantly Japanese 
lifestyle and diet.  Japanese men should be first generation in the US with both 
Japanese parents and grandparents.  
4. Able to meet the requirements of the study; to give voluntary, written informed 
consent; and to adhere to dosing and visit schedules for all 3 periods. 
5. Body mass index (BMI) <35.0 kg/m2 and weight ≥50 kg at screening. 
6. All sexually active subjects of reproductive potential are required to be sexually 
abstinent or use a condom with spermicide when engaging in sexual activity 
throughout the duration of the study and for 90 days after the last dose of study 
drug.
7. Adequate venous access on left or right arm to allow collection of a number of 
blood samples by venipuncture.
8. Adequate hematologic, hepatic, and renal parameters, i.e., hemoglobin >12 g/dL, 
alkaline phosphatase <130 U/L, and creatinine <1.3 mg/dL.
9. Agrees not to donate sperm throughout the study from the first dose of study drug 
to 90 days after the last dose of study drug.
7.2.
Exclusion Criteria
Subjects will be ineligible for the study if they meet any of the following criteria:
1. History of clinically significant renal, hepatic, neurologic, hematologic, 
endocrine, oncologic, pulmonary, immunologic, psychiatric, or cardiovascular 
disease or any other condition that, in the opinion of the PI, could jeopardize the 
safety of the subject or impact the validity of the study results. 
2. Significant gastrointestinal or malabsorption conditions (e.g., history of 
cholecystectomy, gastroparesis, inflammatory bowel disease, pancreatitis, celiac 
disease, sprue, dumping syndrome, intestinal bypass bariatric surgery (lap band 
and gastric sleeve will not exclude subjects), short bowel syndrome, lactose 
intolerance [unless subject avoids dairy products]).  Also, previous surgery or a 


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medical condition that, in the judgment of the PI, may affect absorption, 
distribution, metabolism, or elimination of the drug product (e.g., bariatric 
Roux-en-Y). 
3. Any man in whom testosterone therapy is contraindicated including the following:
a.
Known or suspected carcinoma (or history of carcinoma) of the prostate,
clinically significant symptoms of benign prostatic hyperplasia, and/or clinically 
significant symptoms of lower urinary obstruction and International Prostate 
Symptom Score (IPSS) ≥19. A clinically significant digital rectal examination of 
the prostate (such as irregularities or nodules palpated, or otherwise suspicious 
for carcinoma of the prostate) or clinically significant elevated serum prostate-
specific antigen (PSA) levels (>4.0 ng/mL).  
b. Known or suspected carcinoma (or history of carcinoma) of the breast.
c.
Liver disease defined as alanine aminotransferase (ALT) or aspartate 
aminotransferase (AST) >2 × upper limit of normal (ULN) or 
bilirubin >2 × ULN.
d. Active deep vein thrombosis or thromboembolic disorder, or a 
documented history of these conditions.
e.
Untreated sleep apnea.
f.
Hematocrit >50%.
g. Untreated moderate to severe depression.
4. Current use of long-acting testosterone or any of the testosterone esters 
injectables. 
5. Topical, oral, or injectable testosterone replacement therapy (any kind including 
dehydroepiandrosterone [DHEA] and nutritional supplements) within 28 days
prior to screening; subjects who have used Testopel are excluded if it was used 
within the past 2 years, and subjects who have used AVEED are excluded if it 
was used within the past 6 months.
6. Clinically significant changes in any medications (including dosages) or medical 
conditions in the 28 days before screening.
7. Any significant history of allergy and/or sensitivity to the drug product or its
excipients, including any history of sensitivity to testosterone or testosterone 
esters.
8. Suspected reversible hypogonadism (e.g., leuprolide injection).
9. Is taking concomitant medications that affect testosterone concentrations or 
metabolism (e.g., gonadotropin-releasing hormone [GnRH], 5α-reductase 
corticosteroids, or estradiol; see Section 9.1.2).
10. Uncontrolled diabetes (screening HbA1c ≥9%).
11. Any contraindication to blood sampling.


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12. Intent to have any surgical procedure during the study.
13. Taken any investigational product as part of a clinical study within 30 days or 
5 half-lives of first administration of the investigational product, whichever is 
longer.
14. Donated blood or blood products or experienced significant blood loss within 
90 days before dosing.
15. Donated bone marrow within 6 months before dosing.
16. History of drug or alcohol abuse in the last 6 months or positive result in urine 
drug screen.
17. Ingested St John’s wort within 30 days of screening.
18. Subject currently or planning to be on a special low-fat diet during the study.
19. Clinically significant positive result in virology tests (HIV, hepatitis).
7.3.
Subject Withdrawal and Replacement
Subjects are free to withdraw from the study at any time for any reason. 
In addition, subjects may be withdrawn from the study by the PI or subinvestigator, for 
example in cases of:

Intolerable AEs

Difficulties in blood collection

Protocol violation

ECG abnormality 

Any other clinically significant abnormality as deemed by the PI and/or the 
Sponsor
The clinical study report will include reasons for subject withdrawals as well as details 
relevant to the subject withdrawal. 
Should any subject withdraw or be withdrawn from the study, all the follow-up 
evaluations (Day 31 Exit visit procedures) should be performed. Subjects experiencing 
adverse reactions will be followed until the reaction has resolved. Appropriate 
supportive and/or definitive therapy will be administered as required.
Subjects withdrawn from this study cannot re-enter.  
Subjects who drop out or are withdrawn will be replaced at the discretion of the Sponsor 
in consultation with the PI. 


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Protocol Number: TT-018
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8.
STUDY CONDUCT 
For an overview of test scheduling, see the study design diagram in Figure 1. For a 
detailed description of the study assessments per visit, please refer to the schedule of 
events (Section 2).
8.1.1.
Screening
During the screening period, all prospective subjects will have the study explained in 
non-technical terms by a member of the clinic staff.  The nature of the drug substance to 
be evaluated will be explained together with potential hazards. Subjects will be informed 
of the study restrictions. Prior to performing any study-related procedures on a subject, 
the subject’s acknowledgement of the receipt of this information and his informed 
consent to participate in the study will be obtained in writing. The subject will be given a 
copy of the signed informed consent form (ICF).
Subjects must meet all eligibility and no exclusion criteria before being enrolled in the 
study. 
The following procedures will be performed during screening:

Medical history 

12-lead ECG 

Vital signs, sitting (5 minutes): blood pressure, pulse rate, respiration rate, and 
temperature.  If blood pressure is elevated, repeat at least 5 minutes later per 
site procedures.

Height (centimeters) and weight (kilograms)

Physical examination

Urine drug and alcohol screens

Glycated hemoglobin (HbA1c) determination

Screening determination of testosterone levels (central laboratory): one 
sample at 10 am (± 2 hours), must be less than 350 ng/dL; one repeat sample 
is allowed at least 1 week later if testosterone level is ≥350 ng/dL and 
<400 ng/dL. 

Human immunodeficiency virus (HIV) and hepatitis screens

Fasting clinical laboratory tests (hematology, serum chemistry, urinalysis; see
Section 10.4)

Prostate-specific antigen (PSA)

International Prostate Symptom Score (IPSS) and testosterone deficiency-
specific questionnaires: AMS scale, MSAM-7 (libido questions only), PDQ
(see Appendix 3)


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8.1.2.
Subject Confinement
In Period 1, subjects will be admitted into the study unit on Day -1 prior (Day -2 for first
treatment) to each of the 4 ascending treatment doses. Prior to the first dose of TSX-011, 
subjects will undergo 24-hour blood sampling for endogenous testosterone 
measurements.  Each study subject will remain in the treatment facility from Day -1 until 
after the 24-hour postdose safety evaluation and blood sample collection on Day 2, at 
which time they will be discharged. There will be a washout period of at least 3 days and 
up to 7 days between each dose in Period 1.  
There will be a washout period of at least 3 days and up to 7 days (14 days for initial 
3 subject cohorts) between Periods 1 and 2. In Period 2, subjects will be admitted into 
the study unit from Day -1 to Day 2 and from Day 14 to Day 16. Subjects will return to 
clinic on Day 8 for morning drug dose and for 6-hour postdose blood draw to measure 
testosterone level. After receiving study drug on Day 1 and Day 14, subjects will 
undergo 24-hour PK blood sampling. During these admissions to the study unit, subjects 
will also have assessments of vital signs, physical examination, urine drug/alcohol screen, 
IPSS and testosterone deficiency-specific questionnaires, AEs, concomitant medications, 
and clinical laboratory tests.
In Period 3, Day 16, the subject will leave the study unit with dose adjustment per 
Appendix 2. Subjects will be admitted into the study unit for confinement on Day 29,
undergo PK blood sampling following administration of study drug on Day 30, and be 
discharged on Day 31.  Other assessments during this admission include vital signs, 
physical examination, urine drug/alcohol screen, IPSS and testosterone 
deficiency-specific questionnaires, AEs, concomitant medications, ECG, clinical 
laboratory tests, and PSA.
Subjects may return to the study unit for a safety follow-up visit up to 30 days from 
check-out.
See Section 8.1.3 for duration details if all planned study arms proceed.  
8.1.3.
Study Duration
The approximate duration for each subject in each study period is as follows.
Period 1: One day for each dose, plus a minimum 3-day and maximum 7-day washout 
between each single dose, yielding a minimum of 9 days and a maximum of 21 days from 
first single dose to last.
Periods 2 and 3: A minimum 3-day and maximum 7-day washout (maximum 14-day 
washout for initial 3 subject cohorts) followed by 2 consecutive 15-day dosing periods, 
yielding a minimum of 33 days and a maximum of 37 days (maximum of 44 days for 
initial 3 subject cohorts). 
The study duration (after enrolment) for each subject will be approximately 8 weeks, with 
a range of 6 to 9½ weeks.


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9.
TREATMENT OF SUBJECTS
9.1.1.
Prohibited Food and Beverages
Consumption of foods and beverages containing the following substances are prohibited 
as indicated:

Xanthines / caffeine: 24 hours before dosing and during the study 
confinement period

Alcohol: No more than 3 units per day of alcoholic beverages from the 
beginning of screening through the end of study

Grapefruit / Seville orange: 14 days before dosing and throughout the study 
period

Smokers will be restricted to scheduled smoking breaks during confinement 
days to facilitate conduction of study events

Tribulus alatus plant extracts 
Table 7:
Prohibitions
Prohibition
Metrics for Prohibition
Reason for Prohibition
Classification of 
Reason for
Prohibition 1
Alcohol
No more than 3 units per 
day of alcoholic 
beverages from the 
beginning of screening 
through the EOS; a unit is 
defined as 4 oz of wine, 8 
oz of beer, or 1.5 oz of 
hard liquor
To avoid cognitive 
impairment and study 
subject mistakes in 
following study drug 
administration and 
procedures
Subject compliance 
Grapefruit/Seville 
orange
Prohibited from 14 days 
before dosing and during 
the treatment period
Potential CYP3A 
interaction
Potential CYP3A 
interaction
Herbal supplements 
(particularly those 
affecting testosterone 
levels such as Tribulus 
alatus plant extracts)
Prohibited from 48 hours 
from the beginning of 
screening through the 
EOS
Affecting testosterone 
levels
Affecting 
testosterone levels
St John’s wort
Prohibited from 28 days 
before the first dose of 
study drug through the 
EOS
Potential CYP3A 
interaction
Potential CYP3A 
interaction
CYP = cytochrome P450; EOS = end of study; T = testosterone
1 TSX-011 interaction or confounding effect.


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9.1.2.
Prohibited Medications
Prohibited medications are summarized below.

Any form of testosterone replacement

Finasteride

Dutasteride

St. John’s wort

Luteinizing hormone-releasing hormone (LHRH) agonist or antagonist

Estrogens
9.1.3.
Concomitant Medications
No subject may take medications or herbal products during the study except if allowed by 
the PI.
All medications taken by subjects during the study will be recorded. If drug therapy 
other than that specified in the protocol is required (over the counter and/or prescription), 
a decision to continue or discontinue the subject will be made, based on the time the 
medication was administered and its pharmacology and PK.
9.1.4.
Level of Activity During the Confinement Period
Subjects will remain ambulatory or seated upright for the first 4 hours after drug 
administration, except when they are supine or semi-reclined for study procedures 
(e.g., ECGs). However, should AEs occur at any time, subjects may be placed in an 
appropriate position for comfort or safety. Subjects will not engage in strenuous activity 
at any time during the confinement period. 


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10.
SAFETY ASSESSMENTS
Safety of TSX-011 will be determined by evaluating physical examination findings, 
ECGs, vital signs, clinical laboratory parameters, and AEs (see the Schedules of Events
in Section 2 for details). The PI may order any test at any time for evaluation and 
management of an AE.
Vital signs and ECG assessments have a window of ± 15 minutes around each scheduled 
time point.
If deemed necessary, additional safety measurements will be performed at the discretion 
of the PI.
10.1.
ECGs
For study subjects, 12-lead ECGs will be performed and evaluated for all subjects as
presented in the Schedule of Events (Section 2).
10.2.
Vital Signs
For study subjects, sitting (5 minutes) vital signs including blood pressure, pulse rate, 
respiration rate, and temperature will be evaluated as presented in the Schedule of Events 
(Section 2).
10.3.
Physical Examination
A physical examination will be conducted for all subjects presented in the Schedule of 
Events (Section 2).
The physical examination will include evaluation of the head, eyes, ears, nose, throat, 
neck, heart, chest, lungs, abdomen, genitourinary system, extremities, neurological status, 
and skin.  Digital rectal examination is required only at screening.
10.4.
Clinical Laboratory Tests 
Samples for hematology (excluding HbA1c), serum chemistry (excluding testosterone
and PSA), and urinalysis evaluations will be obtained as presented in the Schedule of 
Events (Section 2).
A certified and accredited facility will perform the safety laboratory tests.  
Laboratory parameters for hematology, serum chemistry, urinalysis, virology, and urine 
drug screen are detailed in Table 7.


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Protocol Number: TT-018
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Table 7:
Clinical Laboratory Tests
Hematology
Serum Chemistry

Hemoglobin

Hematocrit

Total and differential leukocyte count

Red blood cell count

Platelet count

White blood cell count

HbA1c**
Urine drug screen ***

Cocaine 

Cannabinoids 

Alcohol 

Opiates 

Barbiturates 

Amphetamines 

Benzodiazepines
Urinalysis

pH

Specific gravity

Protein

Glucose

Ketones

Bilirubin

Blood

Nitrite

Urobilinogen

Leukocyte esterase

Microscopic assessment for cells and 
casts

Albumin

Alkaline phosphatase

AST

ALT

Blood urea nitrogen

Creatinine

Creatine kinase

Lactate dehydrogenase

Glucose 

Total bilirubin* 

Total protein

Sodium

Potassium

Chloride

Calcium

Triglycerides

Total cholesterol

Uric acid

High-density lipoprotein (HDL)

Low-density lipoprotein (LDL)

Testosterone (per Schedule of Events)

PSA (per Schedule of Events)
Virology

HIV test**

Hepatitis B surface antigen**

Hepatitis C virus**
*
If total bilirubin results are above the upper limits of normal, direct and indirect bilirubin analysis will 
be performed.
** To be performed at screening only.
*** To be performed at screening and at each confinement check-in.
After screening, safety laboratory tests will be performed in the fasted state (at least 8 hours fasted).
10.5.
Adverse Events
This section defines the types of AEs and outlines the procedures for appropriately 
collecting, grading, recording, and reporting them.  Information in this section complies 
with 21 Code of Federal Regulations (CFR) 312, International Conference on 
Harmonisation (ICH) Guideline E2A: Clinical Safety Data Management: Definitions and 
Standards for Expedited Reporting, and ICH Guideline E-6: Guidelines for Good Clinical 
Practice (GCP).


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The investigator is responsible for the detection and documentation of AEs regardless of 
treatment group or suspected causal relationship to the investigational product. For all 
AEs, the investigator must pursue and obtain information adequate to determine the 
outcome of the AE and to assess whether the AE meets the criteria for classification as a
serious adverse event (SAE) or a serious and unexpected suspected adverse reaction 
(SUSAR) requiring immediate notification to the Sponsor or its designated 
representative.
10.5.1.
Definitions of Adverse Events
10.5.1.1.
Adverse Event (AE)
An AE is defined as any untoward or unfavorable medical occurrence associated with the 
subject’s participation in the research, whether or not considered related to the subject’s 
participation in the research (ICH E6 Guidelines for GCP). Any medical condition that is 
present at the time that the subject is screened will be considered as medical history and 
not recorded as an AE; however, if the condition worsens at any time during the study, it 
will be recorded and reported as an AE.
10.5.1.2.
Serious Adverse Event (SAE)
An AE is considered “serious” if, in the view of either the investigator or the Sponsor, it 
results in any of the following outcomes (21 CFR 312.32(a)):

Death:  A death that occurs during the study or that comes to the attention of 
the investigator during the protocol-defined follow-up period must be reported 
to the Sponsor whether it is considered treatment related or not.

A life-threatening event:  An AE or suspected adverse reaction (SAR) is 
considered “life-threatening” if, in the view of either the investigator or the 
Sponsor, its occurrence places the participant at immediate risk of death.  It 
does not include an AE or SAR that, had it occurred in a more severe form, 
might have caused death.

Inpatient hospitalization or prolongation of existing hospitalization.

Persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions.

An important medical event that may not result in death, be life threatening, or 
require hospitalization may be considered an SAE when, based on appropriate 
medical judgment, it may jeopardize the participant and may require medical 
or surgical intervention to prevent one of the outcomes listed above.  
Examples of such medical events include allergic bronchospasm requiring 
intensive treatment in an emergency room or at home, blood dyscrasias or 
convulsions that do not result in inpatient hospitalization, or the development 
of investigational product dependency or abuse.

Congenital anomaly or birth defect.


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If an event meets any of the above definitions, regardless of the severity or relationship of 
the event to the study product, the event must be reported to the Sponsor as described in 
Section 10.5.3.
Adverse events associated with hospitalization or prolongation of hospitalization are 
considered serious. This category also includes transfer within the hospital to an 
acute/intensive care unit (e.g., from a standard of care unit to an acute/intensive care 
unit).
Hospitalization does not include the following:

Rehabilitation facilities, hospice facilities, or respite care (e.g., caregiver relief)

Emergency room visits

Same day surgeries (as outpatient/same day/ambulatory procedures)

<24 hour admissions for observation or evaluation
Hospitalization or prolongation of hospitalization in the absence of a precipitating, 
clinical AE is not in itself an SAE.  Examples include:

Admission for treatment of a preexisting condition that did not worsen

Protocol-specified admission (e.g., for a procedure required by the study protocol)

Hospitalizations for cosmetic elective surgery, social, and/or convenience 
admissions

Pre-planned treatments or surgical procedures should be noted in the baseline 
documentation for the individual subject.
Medical and scientific judgment should be exercised in other situations, such as 
important medical events that may not be immediately life-threatening or result in death 
or hospitalization but may jeopardize the patient or may require intervention to prevent 
one of the other outcomes listed in the above definition. These should also usually be 
considered serious, and reported.
10.5.1.3.
Serious and Unexpected Suspected Adverse Reactions (SUSARs)
Suspected adverse reaction (SAR) means any AE for which there is a reasonable 
possibility that the study drug caused the AE.  For the purposes of safety reporting, 
“reasonable possibility” means there is evidence to suggest a causal relationship between 
the study drug and the AE.  A SAR implies a lesser degree of certainty about causality 
than an ADR (21 CFR 312.32(a)). 
The Sponsor is responsible for assessing AEs for expectedness.  With regards to reporting 
to the Health Authority, an AE is considered “unexpected” when its nature (specificity), 
severity, or rate of occurrence is not consistent with applicable product information as 
described in the safety information provided in the protocol/package insert/investigator’s 
brochure/prescribing information for the study drug. “Unexpected,” as used in this 
definition, also refers to AEs or SARs that are mentioned in the investigator’s brochure as 


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occurring with a class of drug or as anticipated from the pharmacological properties of 
the study drug but are not specifically mentioned as occurring with the particular study 
drug under investigation (21 CFR 312.32(a)). 
For a comparator product with a marketing authorization, the expectedness of an AE will 
be determined by whether or not it is listed in the Prescribing Information. 
Adverse events that meet all three criteria (i.e., serious, unexpected and SAR; SUSAR)
are reported to FDA as described in Section 10.5.3.3. 
10.5.2.
Adverse Event Monitoring
Adverse events will be continually monitored for the duration of the study. During 
confinement, subjects will be monitored throughout confinement until the poststudy 
follow-up visit for adverse reactions to the study formulation and/or procedures. Subjects
will be asked an open question, such as “How have you been feeling since you were last 
asked?” at the following time points:

Period 1: predose (Day 1), 24 hours post dose (Day 2), and for each 
ascending dose

Period 2: Day 1 predose, Day 8 postdose, and Day 15 post dose

Period 3: Day 19 postdose, and Day 30 after last dose 
The subjects will also be instructed to inform the PI/investigator’s designee or clinic staff 
of any AEs and undercurrent illnesses experienced during the study. 
All AEs ongoing at the follow-up visit will be followed up until resolution, stabilization, 
or determination that the subject is lost to follow-up (for up to 30 days) by the 
investigator or designee.  Unresolved AEs at the follow-up visit will be followed up for a 
further 30 days. For AE status to be considered lost to follow-up, the site must attempt to 
contact the subject by phone twice, followed by a registered letter; if no contact is made 
within 5 days of receipt of the registered letter or return of the letter as undeliverable, a 
status of lost to follow-up is entered. 
A physician will administer treatment for AEs and/or SAEs as appropriate.
10.5.3.
Reporting Adverse Events (AEs), Serious Adverse Events (SAEs) and 
Suspected Unexpected Serious Adverse Reactions (SUSARS)
10.5.3.1.
Reporting Adverse Event (AEs)
All AEs occurring from signature of the informed consent until completion of the clinical 
study will be recorded in the case report form (CRF) and coded using the most recent 
version of the Medical Dictionary of Regulatory Activities (MedDRA®).
An AE is any unwarranted medical occurrence in a patient or clinical investigation 
patient administered a pharmaceutical product that does not necessarily have a causal 
relationship with this treatment (ICH/World Health Organization [WHO]). Therefore, an 
AE can be any unfavorable and unintended sign (including an abnormal laboratory 


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finding, for example), symptom, or disease temporally associated with the use of a 
medical product, whether or not considered related to the medical product (ICH/WHO).
The investigator will make a determination of the relationship of the AE to the study drug 
using a 4-category system (not related, possible, probable, and definite) according to the 
guidelines in Table 8.
Table 8:
Relationship to Study Drug
Not Related
An AE that does not follow a reasonable temporal sequence from 
administration of the drug or that can be reasonably explained by other 
factors, including underlying disease, complications, concomitant drugs, or 
concurrent treatment.
Possible
The AE follows a reasonable temporal sequence from drug administration; 
is unlikely to have been produced by the patient’s underlying medical 
conditions, environmental or toxic factors or other therapeutic interventions.
Probable
The AE follows a reasonable temporal sequence from drug administration, 
or is associated with established drug concentration in body tissues; 
improves on stopping or reducing drug dosage (de-challenge); and could not 
reasonably be explained by the study patient's underlying medical 
conditions, environmental or toxic factors, or other therapeutic 
interventions.
Definite
Same as for “probable” - but AE reappears on repeated exposure 
(re-challenge).
Each sign or symptom reported will be graded on a 3-point severity scale (mild, 
moderate, or severe), according to Table 9.
Table 9:
Severity Scale
Mild
(Grade 1)
Experience is minor and does not cause significant discomfort to 
subject/patient or change in activities of daily living (ADLs); subject/patient is 
aware of symptoms but symptoms are easily tolerated.
Moderate
(Grade 2)
Experience is an inconvenience or concern to the patient and causes 
interference with ADLs but the patient is able to continue with ADLs.
Severe
(Grade 3)
Experience significantly interferes with ADLs and the patient is incapacitated 
and/or unable to continue with ADLs. 
Note: An experience may be severe but may not be serious (e.g., severe 
headache).
The date and time of onset, duration, and outcome (resolved, improved, unchanged, 
worse, fatal, or unknown/lost to follow-up) of each event will be noted. 


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10.5.3.2.
Reporting Serious Adverse Events (SAEs)
Safety reporting, including suspected “unexpected” serious adverse reactions (SUSARs) 
reporting, will be performed in line with European Clinical Trial Directive (2001/20/EC)
and United Kingdom guidelines, as applicable.
If an SAE occurs to a patient on this study, the Sponsor will be contacted and SAEs will 
be reported to the appropriate regulatory authority in accordance with local laws and 
regulations and in accordance with site standard operating procedures (SOPs).
All SAEs will be reported to the contract research organization (CRO), and subsequently
in redacted format to Sponsor, the Medical Monitor, and Rho, Inc., which is acting on 
behalf of the Sponsor as the holder of the safety database.  All SAEs must be 
communicated within 24 hours and followed by written reports within 48 hours of first 
knowledge of the event, whether or not the SAEs are deemed drug related. 
A paper SAE report form will be submitted to the following as a fax or as a scan that is 
emailed. The initial SAE notification should provide the following information:

Study number

Subject number

Gender

Date of birth

PI or designated physician name and investigational site address

Date of SAE onset

Details of SAE

Criterion of SAE classification

Study drug name, or code if blinded

Treatment start date

Causality assessment
Initial reports of SAEs must be later followed with detailed descriptions, including 
photocopies of other documents where applicable (e.g., hospital reports, laboratory 
reports, hospital consultant reports, autopsy reports, etc.) with the subject’s personal 
identifiers removed. All relevant information obtained by the PI will be reviewed and as 
appropriate recorded in the subject’s CRF or where applicable, and a new SAE form will 
be generated. 
10.5.3.3.
Reporting Suspected Unexpected Serious Adverse Reactions (SUSARS)
If applicable, the Sponsor must ensure that the research ethics committee (REC), the 
appropriate Competent Authority, and the licensing authority are informed of all 
SUSARs within 15 days of the event in accordance with Directive 2001/20/EC. All 
SUSARs leading to death or which are life-threatening should be reported by the Sponsor 


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to the REC, the appropriate Competent Authority, and the licensing authority within 7 
days of the event. The Sponsor should present all SUSARs to the appropriate Competent 
Authority once a year, or on request. 
This activity is delegated by the Sponsor to the CRO. In the event of a SUSAR, the CRO 
will submit the relevant data to the REC and the Medicines and Healthcare Products 
Regulatory Agency (MHRA).
10.5.4.
Pregnancy Reporting
If any study subject’s female partner becomes pregnant while the study participant is 
enrolled in the study or within 90 days following the last dose, the PI should submit a 
pregnancy report form within 24 hours of the PI becoming aware of the pregnancy 
confirmation. 
If permission is granted, pregnancies will be followed up by the PI. If the pregnancy is to 
be terminated, the date of termination should be provided. If the pregnancy ends for any 
reason before the anticipated date, the PI will notify the Sponsor immediately.
If the PI becomes aware of an AE (maternal or infant), a birth defect/congenital 
abnormality, or other adverse pregnancy outcome (e.g., miscarriage or stillbirth) that 
occurred during pregnancy or delivery and that fulfills the definition of a SAE, the PI 
should complete and submit a SAE report form.
Following birth, the progress of any live infants, where permissible, will be followed as 
deemed appropriate by the PI.


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11.
PHARMACOKINETIC ASSESSMENTS
11.1.
PK Blood Samples
Blood samples for PK will be collected according to the schedule of events in blood 
collection tubes as detailed in the laboratory manual. All PK blood samples will be 
collected for central bioanalytical laboratory analysis.  The initial cohort of 3 subjects 
will have additional PK samples taken.  Specifically, duplicate PK samples (one serum 
and one plasma) will be taken prior to each dose (i.e., 0 hr) and at each postdose 
collection point following all 4 period 1 doses and analyzed per instructions in the lab 
manual. 
In addition, the second and third cohorts of 3 subjects each will have duplicate PK 
samples taken prior to the 570 mg TU dose and postdose collection points following the 
instructions in the lab manual. The serum sample shall be processed initially, and only if 
TU is detectable at a level 5 times above the LLOQ (i.e. 10 ng/ml) shall the enzyme 
inhibited plasma sample undergo PK analysis.
Period 1: Blood samples for the determination of endogenous testosterone and DHT (4-
6 mL per time point) will be collected for a single 24-hour period before any study 
subject exposure to TSX-011.  This baseline assessment of endogenous testosterone and 
DHT will be assessed over a 24-hour predose interval (Day -1) at 0, 1.5, 3, 4.5, 6, 8, 12, 
16, and 24 hours. 
Blood samples (4-6 mL per time point) for 24-hour post-dosing will be collected on Day 
1 of each dosing PK (190, 380, 570 mg TU) at 0, 1.5, 3, 4.5, 6, 8, 12, 16, and 24 hours.
Period 2: Blood samples (4-6 mL per time point) for determination of PK measurements
will be collected at 0, 1.5, 3, 4.5, 6, 8, 10, 11.5, 13, 14.5, 16, 18, and 24 hours on Day 1 
and Day 15. The three initial cohorts of 3 subjects each will have additional PK samples 
taken.  Specifically, duplicate PK samples (one serum and one plasma) will be taken on 
Day 8 prior to dosing and at 6 hours (± 15 minutes) after the morning dose. The plasma 
sample values will be used to dose titrate according to the adaptive dosing design 
(Appendix 2).  
For the first cohort, if TU is detectable at a level 5 times above the LLOQ (i.e. 10 ng/ml) 
in the previously collected Day 8 samples, then for PK assessments on Day 15, all blood 
samples will be collected in duplicate (one serum and one plasma).  
For the second and third cohorts, Day 15 samples will be collected in duplicate.  The 
serum sample shall be processed initially, and only if TU is detectable at a level 5 times 
above the LLOQ (i.e. 10 ng/ml) shall the enzyme inhibited plasma sample undergo PK 
analysis.
Period 3: 
On Day 30, PK samples for a 24-hour PK profile will be obtained at the following 
sampling times based upon the daily dosing regimen.


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For subjects on once daily dosing, blood samples for determination of PK measurements 
(4-6 mL blood per time point) will be collected at 0, 1.5, 3, 4.5, 6, 8, 12, 16, and 24 
hours.
For subjects on twice daily dosing, blood samples for determination of PK measurements
(4-6 mL blood per time point) will be collected at 0, 1.5, 3, 4.5, 6, 8, 10, 11.5, 13, 14.5, 
16, 18, and 24 hours.
For subjects on thrice daily dosing, blood samples for PK determination will be collected 
at 0, 1.5, 3, 4.5, 6, 8, 9.5, 11, 12.5, 14, 15.5, 17, 18.5, 20, and 24 hours.
The three initial cohorts of 3 subjects each will have additional PK samples taken.  
Specifically, duplicate PK samples (one serum and one plasma) will be taken on Day 19
at 6 hours (± 15 minutes) after the morning dose.  The plasma sample values will be used 
to dose titrate according to the adaptive dosing design (Appendix 2).  
For the first cohort, if TU is detectable at a level 5 times above the LLOQ (i.e. 10 ng/ml) 
in the previously collected Day 19 samples, then for PK assessments on Day 30, all blood 
samples will be collected in duplicate (one serum and one plasma).  
For the second and third cohorts, Day 30 samples will be collected in duplicate.  The 
serum sample shall be processed initially, and only if TU is detectable at a level 5 times 
above the LLOQ (i.e. 10 ng/ml) shall the enzyme inhibited plasma sample undergo PK 
analysis.  
A dosing window of ± 60 minutes is allowed; however, this window establishes time 0 
and subsequent sampling times will be followed as indicated above.  For example, if 
subject is dosed at 7:45 am, this is time 0; 1 hour postdose is 8:45 am and so on.
The exact time the PK blood sample is obtained must be recorded.  PK samples should be 
taken as close to their allotted sampling times as practical to minimize bias in the baseline 
corrected PK parameters; however a window of ± 15 minutes will be permitted.
Cannulae may be used for blood sample withdrawal. Before withdrawing blood for PK, 
the cannula must be aspirated to permit removal of the “dead space” blood, which is 
discarded, and then the PK blood may be withdrawn using a new syringe.
The actual times of each sample draw will be recorded to the nearest minute. The 
recorded actual sample times will be used in conjunction with the actual time of dose 
administration for calculation of PK parameters as appropriate, as denoted above.
11.2.
Blood Volume, Pharmacokinetic Blood Sample Processing/
Analysis, and Bioanalytical Method
Total blood volumes per individual subject, PK blood sample processing and analysis, 
and bioanalytical methods in each study period are detailed in the laboratory manual.


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12.
EXPLORATORY ASSESSMENTS
The exploratory assessments of the study are: 
1) measurements of QOL related to hypogonadal symptoms. These QOL 
questionnaires include the IPSS, AMS scale, MSAM-7 (libido questions only), and PDQ, 
and are administered as follows.

Screening

Period 2: Day -1, Day 15

Period 3: Day 31
2) To determine the preferred method of PK specimen collection
Serum or enzyme 
inhibited plasma. Method of PK collection (serum vs enzyme inhibited plasma) shall be 
performed to assess consistency of bioanalytical assay reporting.


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13.
STUDY DRUG MATERIALS AND MANAGEMENT
13.1.
Investigational Products
TSX-011
Active ingredient: testosterone undecanoate USP
Example approximate doses: 
(190 mg TU) 3 × 63.2 mg TSX-011 capsule
(380 mg TU) 6 × 63.2 mg TSX-011 capsule
(570 mg TU) 9 × 63.2 mg TSX-011 capsule
13.2.
Drug Identification
The TSX-011 formulation will be composed of pharmaceutical grade synthetic 
testosterone undecanoate USP powder purchased from Pfizer (Kalamazoo, MI), which
maintains a Drug Master File with the FDA containing stability data for testosterone drug 
substance.  The excipients used in the manufacture of the encapsulated TSX-011
formulation are distearoylphosphatidylcholine (DSPC), microcrystalline cellulose 
National Formulary (NF), sodium starch glycolate NF, and alcohol USP.  The excipients 
used in the enteric coating are methacrylic acid copolymer NF, triethyl citrate NF, talc 
NF, and purified water USP.  Alcohol and purified water are removed during processing.  
13.3.
Drug Supply 
Please refer to the pharmacy manual.
13.4.
Drug Accountability, Storage, and Retention
The study site must maintain accurate records demonstrating dates and amount of study 
treatment dispensed (patient-by-patient accounting) and accounts of any study treatment 
accidentally or deliberately destroyed.  
Unless otherwise notified, all drug products, including the empty packaging if applicable,
must be saved for study treatment accountability.  At the end of the study, reconciliation 
must be made between the amount of study treatment supplied, dispensed, and 
subsequently destroyed or returned to TesoRx Pharma LLC.  A written explanation will 
be provided for any discrepancies.
At the conclusion of the study, any unused study drug in addition to used and unused 
packaging will be returned to the Sponsor. 


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13.5.
Randomization and Blinding
13.5.1.
Randomization:  Based on Day 8 Testosterone Level
If Period 2 Day 8 (6 hours postdose ± 15 minutes) total testosterone is >800 ng/dL, 
subjects will be randomized in a 1:1 ratio to receive:
o
Schedule A:  317 mg (TU) TSX-011 twice daily OR
o
Schedule B:  507 mg (TU) TSX-011 once daily
Subjects will be stratified during randomization per Japanese/non-Japanese classification.  
Enrolment will be managed to result in at least 10 evaluable Japanese subjects.  
Stratification and randomization will be managed within the electronic data capture 
system. 
The study is an open-label study, and as such, no blinding will be performed.
13.6.
Dosage and Administration
TSX-011 capsule(s) will be administered orally with at least 240 mL of water. The 
drinking containers will be examined by the clinic staff immediately after dosing to 
ensure all study drug and water was taken. Dosing (swallowing capsules) should be 
completed within 5 minutes of starting.  Study drug containers will be returned to the 
pharmacy after dosing is complete. All drug administration procedures will be performed 
at the clinical study unit during confinement. The actual time of each dose administration 
will be recorded to the nearest minute, and this will be used in conjunction with the actual 
sample times to determine PK parameters as appropriate.
13.7.
Meal Schedule
Meals and/or snacks will be provided as appropriate (breakfast, lunch, and dinner) on
predose days (e.g., Day -1); thereafter, the meal schedule will be as follows.
Subjects under fed conditions will be dosed after at least one hour fasted and 15 minutes 
before a standard reference meal (30% fat), except for Period 1, 190 mg dose fasted, 
which will be dosed after an overnight fast of at least 6 hours duration, and no food for 
2 hours after dosing. Standard reference (30% fat) meals will be provided at no sooner 
than 15 minutes after dosing, and at appropriate times thereafter. During housing, 
postdose meal plans will be consistent for all periods.
In Period 3, subjects assigned to a twice-daily dosing regimen may have a standard snack
(e.g., granola bar) between 2:00 and 3:00 pm (e.g., if 8:00 am dosing).  The study 
subjects randomized to the thrice-daily dosing schedule may have a snack (e.g., fruit) no 
sooner than 2 hours after dosing (e.g., between 4:00 and 5:00 pm if 2:00 pm dosing).
Foods and beverages containing alcohol, caffeine, or grapefruit will not be served in the 
clinic during any study part.


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13.8.
Water Administration
Water/liquid will not be allowed to be consumed (except for study drug administration) 
in the study facility from 1 hour before dosing until 1 hour post dosing in all study arms;
thereafter, subjects can consume water freely.


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14.
STATISTICS
Detailed methodology for summary and statistical analyses of the data collected in this 
study will be documented in a statistical analysis plan (SAP). 
Interim review of safety and efficacy of TSX-011 for the initial 9 subjects will occur 
prior to enrolment of the remaining subjects in the study.
The SAP will be prepared by an appropriate vendor, agreed upon with the Sponsor, and 
finalized before database lock. 
This document may modify the plans outlined in the protocol; however, any major 
modifications of the primary endpoint’s definition and/or analysis will also be reflected in 
a protocol amendment. Additional statistical analyses other than those described in this 
section may be performed, if deemed appropriate, and included in the plan. 
14.1.
Sample Size Calculation
The study is a proof-of-concept study with adaptive dosing.  The sample size chosen for 
this study was selected without statistical considerations but has been determined 
adequate to meet the study objectives.
14.2.
Analysis Populations
The analysis populations are defined as follows:

The Safety population is defined as all randomized subjects who received at least 
one dose of study drug and have at least one post-baseline safety assessment.

The PK population is defined as all randomized subjects for whom at least one PK 
parameter of interest can be calculated.  In general, on a parameter-by-parameter 
basis, an individual subject’s data may be excluded from analysis if insufficient 
data are available for that subject to calculate the specific parameter in question.

The clinical batch population is defined as all enrolled subjects for whom at least 
one PK parameter can be calculated.  This population will be stratified by dosed 
clinical study drug batch (e.g. first, second batch).  
14.3.
Statistical Analyses
14.3.1.
Safety Analyses
Safety data including laboratory evaluations, physical examinations, AEs, standard 
12-lead ECG parameters, and vital signs assessments will be summarized by treatment 
group and time point of collection, when appropriate. 
Adverse events will be coded using the most recent version of MedDRA. A by-patient 
AE listing by MedDRA system organ class and by preferred term within system organ 
class, including verbatim term, dose level, severity, and relationship to treatment, will be 
provided. This listing will include all AEs and SAEs.


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Descriptive statistics (arithmetic mean, standard deviation [SD], coefficient of variation 
[CV], median, minimum, and maximum) will be calculated for quantitative safety data as 
well as for the difference from baseline, when appropriate.
Tables summarizing shifts in clinical laboratory results with respect to normal range will 
be provided, as well as tables summarizing shifts in vital signs and standard 12-lead 
ECGs with respect to normal and abnormal results.
Concomitant medications will be listed by treatment and coded using the most recent 
version of the World Health Organization Drug Dictionary.
14.4.
Pharmacokinetic Analyses
14.4.1.
Pharmacokinetic Parameters
The following PK parameters will be calculated using both actual and/or BC testosterone, 
free testosterone, TU, DHTU, and DHT concentrations following dose administration of 
TSX-011:
AUCt:
The area under the concentration versus time curve, from time 0 to the last 
measurable concentration on or before time t, as calculated by a linear 
trapezoidal method.
BC:
Baseline-corrected T of single-dose data in Period 1. For AUC, this is the 
total AUC after each dose subtracted from the corresponding total AUC of 
endogenous testosterone. For estimation of z, t½, CL/F, and Vss/F, the 
discrete total endogenous testosterone concentrations are first subtracted 
from total testosterone concentrations obtained at the same nominal time 
point after single-dose TSX-011. Differences of zero or less than zero are 
ignored in this determination.
Cmax:
Maximum measured concentration over the time span specified.
Cavg:
Average measured concentration over the time span specified.
Cmin:
Minimum measured concentration over the time span specified.
Tmax:
Time of the maximum measured concentration. If the maximum value 
occurs at more than one time point, Tmax is defined as the first time point 
with this value.
CL/F:
The apparent total body clearance (measured for BC testosterone only).
Vss/F:
Total steady-state volume of distribution (measured for BC testosterone
only).
z:
Apparent terminal elimination rate constant calculated from a semi-log plot 
of the single-dose BC testosterone concentration versus time curve. The 
parameter will be calculated by linear least-squares regression analysis 
using the maximum number of points in the terminal log-linear phase (e.g.,
3 or more non-zero serum concentrations).
t½:
Apparent terminal elimination half-life will be calculated as 0.693/z
(measured for BC testosterone only).


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Tmin:
Time of the minimum measured concentration.  If the minimum value 
occurs at more than one time point, Tmin is defined as the first time point 
with this value.
For all study arms, other PK parameters may be calculated and will be appropriately 
described in the SAP.
14.4.2.
Method for Baseline-Adjustment of Pharmacokinetic Parameters
An adjustment will be made on every serum testosterone, free testosterone, and DHT 
concentrations as follows: BC testosterone of single-dose data in Period 1. For AUC this 
is the total AUC after each dose subtracted from the corresponding total AUC of 
endogenous testosterone. For estimation of z, t½, CL/F, and Vss/F, the discreet total 
endogenous testosterone concentrations are first subtracted from total endogenous
testosterone concentrations obtained at the same nominal time point at the baseline PK 
determined at Period 1. Differences of zero or less than zero are ignored in this 
determination.
This adjustment is hence subject- and period-specific.
14.4.3.
Pharmacokinetic Data Analyses
Details of the PK data analyses are specified in the SAP.  An overview of the data 
analysis is provided below.  
The PK sample concentrations for all subjects within each dose level and dosing regimen 
will be summarized for each nominal sample time using min, max, median, mean (SD), 
and geometric mean (confidence interval [CI]).  
Noncompartmental analysis will be performed on serum free testosterone, total
testosterone, TU, DHT, and DHTU levels using the actual recorded time of sample 
withdrawals. The following actual PK parameters for serum testosterone, free
testosterone, TU, DHT, and DHTU following single-dose administration of TSX-011 will 
be calculated: AUC, Cmax, Cmin (actual testosterone), Tmax, and Tmin. Baseline-corrected 
values for testosterone, free testosterone, and DHT will also be calculated using the same 
PK parameters.  In addition, BC z and t½ will be collected for testosterone, free 
testosterone, and DHT.  In addition, the fraction of time within the therapeutic window 
and the fraction of time above the therapeutic threshold will be reported for Period 2, 
Day 15 and Period 3, Day 30.
Pharmacokinetic parameters from Periods 1, 2, and 3 will be summarized using statistics 
appropriate for the PK parameter (means, geometric means, frequencies, etc.). 
Continuous PK parameters will also be summarized using least squares means or least 
squares geometric means estimated using mixed models statistical analyses.
Dose proportionality of the BC PK parameters: AUCs and Cmax will be assessed among 
the once-daily dosing regimens of Period 1 using the CI criteria (Smith et al., 2000). 


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15.
STUDY ADMINISTRATION
15.1.
Basic Principles
This research will be carried out in accordance with the principles enunciated in the 
Declaration of Helsinki (Seoul 2008), the ICH harmonized tripartite guideline regarding 
GCP (E6 Consolidated Guidance, April 1996), and the SOPs of clinical sites.
15.2.
Data Capture
A customized electronic source data capture system will be developed and used.  Each 
electronic source data capture form will be reviewed and approved by the PI. The CRO
will ensure complete and accurate entries on the forms.
15.3.
Study Report
The final report will be written according to the ICH E3 Guideline (Structure and Content 
of Clinical Study Reports).  The report includes a description of the clinical conduct of 
the study, analytical methods and results, and the statistical analysis of the PK and safety 
parameters described in the statistical methodology section of the protocol.
15.4.
Confidentiality
All members of the PI’s staff will sign confidentiality agreements with the CRO.  All 
information provided to the PI dealing with the study and all information obtained during 
the course of the study will be regarded by CRO as confidential. Subjects will be 
informed that all study findings will be stored on computers and handled in a strictly 
confidential way.  Subjects will be identified throughout documentation and evaluation 
by the individual subject number and initials (where appropriate), whereas all subjects’ 
names will be kept secret. The PI must guarantee the privacy of the subjects taking part 
in the study.  Any information concerning the volunteers (clinical notes, identification 
codes, etc.) must be kept on file by the PI, who will ensure that it is revealed only to the 
applicable regulatory authorities and to the Sponsor and its designated agent for the 
purposes of study monitoring, auditing, or official inspections.
15.5.
Publication Policy
All data generated by this study are considered confidential information and the property 
of the Sponsor. This confidential information may be published only with the Sponsor's 
written agreement and in collaboration with participating personnel from the Sponsor.
15.6.
Procedure for Amendments to Protocol
No deviations from this protocol will be permitted, except in a medical emergency, 
without the approval of the Sponsor and the institutional review board (IRB). The PI and 
the Sponsor will discuss any amendment to this study. If an agreement is reached 
concerning the need for modification, this agreement will be made in a formal 


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amendment to the protocol. Any protocol amendments must be reviewed by the Sponsor, 
the PI, applicable regulatory authorities, and the IRB.
The IRB must approve all revisions and/or amendments to the protocol in writing. 
15.7.
Institutional Review Board 
This protocol, ICFs, and any amendments to the protocol will be reviewed by the IRB 
and the study will not start until the committee has approved the protocol or a 
modification thereof.  The committee is constituted and operates in accordance with the 
principles and requirements described in the ICH harmonized tripartite guideline 
regarding GCP (E6 Consolidated Guidance, April 1996). Notice that the protocol and 
informed consent have been reviewed and approved by the IRB and will be in the final 
study report.
15.8.
Termination of Study
The Sponsor reserves the right to discontinue this study for administrative reasons at any 
time. The PI, in collaboration with the Sponsor, reserves the right to discontinue the 
study for safety reasons at any time.
15.9.
Study Records
All raw data generated in connection with this study, together with the original copy of 
the final report, will be retained in the archives of the CRO or designee until at least 
5 years after the last approval of a marketing application in an ICH region and until there 
are no pending or contemplated marketing applications in a ICH region, or at least 
5 years have elapsed since the formal discontinuation of clinical development of the 
investigational product. However, these documents should be retained for a longer 
period if required by applicable regulatory requirements or by agreement with the 
Sponsor. It is the responsibility of the Sponsor to inform the CRO as to when these 
documents no longer need to be retained.
15.10.
Quality Assurance/Quality Control
The study will be conducted in compliance with ICH GCP and all local laws and 
regulations. Standard operating procedures will be adhered to for all activities relevant to 
the quality of the study. All clinical data will undergo 100% monitoring prior to clinical 
database lock.  Edit checks will then be performed as a validation routine using SAS to 
check for missing data, data inconsistencies, data ranges, etc.  Corrections will be made 
prior to database lock.


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16.
REFERENCES
1. Hirano K, Hunt CA. Lymphatic transport of liposome-encapsulated agents: 
effects of liposome size following intraperitoneal administration. J Pharm Sci. 
1985 Sep;74(9):915-21.
2. Varshosaz J, Minayian M, Moazen E. Enhancement of oral bioavailability of 
pentoxifylline by solid lipid nanoparticles. J Liposome Res. 2010 
Jun;20(2):115-23.
3. Investigator’s Brochure, Version Number: V1.0 Release Date: 31 August 2011.
4. Rowe RC, Sheskey PJ, Quinn ME, eds. Handbook of Pharmaceutical Excipients.  
6th ed. Washington, DC: Pharmaceutical Press, 2009.
5. Schuirmann DJ. A comparison of the two one-sided tests procedure and the power 
approach for assessing the equivalence of average bioavailability. J 
Pharmacokinet Biopharm. 1987 Dec;15(6):657-80.
6. CENTER FOR DRUG EVALUATION AND RESEARCH. APPLICATION 
NUMBER: 022219Orig1s000 PHARMACOLOGY REVIEW(S)
7.
Heineman LAJ, Saad F, Zimmerman T, et al. The Aging Males' Symptoms 
(AMS) scale: update and compilation of international versions. Health Qual Life 
Outcomes. 2003 May 1;1:15.
8.
Lee KK, Berman N, Alexander GM, Hull L, Swerdloff RS, Wang C. A simple 
self-reported diary for assessing psychosexual function in hypogonadal men. J 
Androl. 2003 Sep-Oct;24(5):688-98.
9. Smith, Brian P., et al., 2000.  Confidence interval criteria for assessment of dose 
proportionality.  Pharm. Research 17(10): 1278-83.


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APPENDIX 1.
INTERNATIONAL PROSTATE SYMPTOM SCORE 
(IPSS)
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
Score
Incomplete Emptying
Over the past month, how often have you had a 
sensation of not emptying your bladder completely 
after you finish urinating?
0
1
2
3
4
5
Frequency
Over the past month, how often have you had to 
urinate again less than two hours after you finish 
urinating?
0
1
2
3
4
5
Intermittency
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
Urgency
Over the past month, how difficult have you found 
it to postpone urination?
0
1
2
3
4
5
Weak stream
Over the past month, how often have you had a 
weak urinary stream?
0
1
2
3
4
5
Straining
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 times or 
more
Score
Nocturia
Over the past month, how many times did you most 
typically get up to urinate from the time you went to 
bed until the time you got up in the morning?
0
1
2
3
4
5
Total IPSS Score
Quality of life due to urinary 
symptoms
Delighted
Pleased
Mostly satisfied
Mixed - about 
equally satisfied 
and dissatisfied
Mostly 
dissatisfied
Unhappy
Terrible
If you were to spend the rest of your life with your 
urinary condition the way it is now, how would you 
feel about that?
0
1
2
3
4
5
6
Total score:
0 7 
mildly symptomatic
8 19 
moderately symptomatic
20 35 
severely symptomatic


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APPENDIX 2.
ADAPTIVE DOSING CRITERIA
Table 10 summarizes the adaptive design and adjustment criteria. 
If the total testosterone subject report is delayed past the dose adjustment day, the subject 
should remain on the existing dose until availability of the new testosterone value.  
Dose adjustment number 1 (Period 3, Day 16):
In Period 2, the subjects will receive 380 mg of TSX-011 twice daily (8 am ± 60 minutes 
and 10 hours after morning dose) under fed conditions for 15 days.
If Period 2 Day 8 (6 hours postdose ± 15 minutes) total testosterone is <350 ng/dL, adjust 
dose to 570 mg (TU) TSX-011 twice daily.
If Period 2 Day 8 (6 hours postdose ± 15 minutes) total testosterone is ≥350 ng/dL and 
<500 ng/dL, adjust dose to 443 mg (TU) TSX-011 twice daily.
If Period 2 Day 8 (6 hours postdose ± 15 minutes) total testosterone is 500 to 800 ng/dL,
inclusive, maintain 380 mg (TU) TSX-011 twice daily.
If Period 2 Day 8 (6 hours postdose ± 15 minutes) total testosterone is >800 ng/dL, 
randomize subjects in a 1:1 ratio to receive:
o
Schedule A:  317 mg (TU) TSX-011 twice daily OR
o
Schedule B:  507 mg (TU) TSX-011 once daily.
Subjects will be stratified during randomization per Japanese/non-Japanese classification.  
Stratification and randomization will be managed within the electronic data capture 
system. 
If imbalance in randomization occurs, study subjects may be manually assigned to 
schedule A or B to balance dosing schedule.
Dose adjustment number 2 (Day 26):
If Period 3 Day 19 (6 hours postdose ± 15 minutes) total testosterone is <350 ng/dL, dose 
adjust subjects to 570 mg TU dosing thrice daily.  Dosing times should be (8 am
± 60 minutes, 8 hours post morning dose ± 15 minutes, and 14 hours post morning dose 
± 15 minutes):
If Period 3 Day 19 (6 hours postdose ± 15 minutes) total testosterone is ≥350 ng/dL and 
<500 ng/dL:
a.
Dose adjust subjects on once-daily dosing from 507 mg TU daily to 570 mg
TU daily. 
b.
Dose adjust subjects on twice daily dosing as follows:
o
If dose is 570 mg TU twice daily, increase to 633 mg TU twice daily.
o
If dose is 443 mg TU twice daily, increase to 507 mg TU twice daily.
o
If dose is 380 mg TU twice daily, increase to 443 mg TU twice daily.
o
If dose is 317 mg TU twice daily, increase to 380 mg TU twice daily.


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If Period 3 Day 19 (6 hours postdose ± 15 minutes) total testosterone is 500 to 800 ng/dL 
inclusive, continue current dose.
If Period 3 Day 19 (6 hours postdose ± 15 minutes) total testosterone is >800 ng/dL, 
decrease TSX-011 dose as follows:
a.
Dose-adjust subjects on once-daily dosing from 507 mg TU daily to 
380 mg TU daily.
b. For the twice-daily dosing group:
o
If dose is 570 mg TU twice daily, decrease to 507 mg TU twice daily.
o
If dose is 443 mg TU twice daily, decrease to 380 mg TU twice daily. 
o
If dose is 380 mg TU twice daily, decrease to 317 mg TU twice daily. 
o
If dose is 317 mg TU twice daily, decrease to 253 mg TU twice daily. 


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Table 10:
Adaptive Design and Dose Adjustment Criteria
Period 2 - Days 1-15
Period 2 - Dose Adjustment on Day 16
Day 8 T level 
(ng/dL)
Starting 
Dose
Frequency
Dose Change
New Dose
Frequency
<350
380
BID
Increase
570
BID
350-499
380
BID
Increase
443
BID
500-800
380
BID
No change
380
BID
>800
380
BID
Decrease
(randomization 1:1)
317
BID
>800
380
BID
Decrease
(randomization 1:1)
507
QD
Period 3 - Day 16-30
Period 3 - Dose Adjustment on Day 26
Day 19 T level
(ng/dL)
Starting 
Dose
Frequency
Dose Change
New Dose
Frequency
<350
all
Increase
570
TID
350-499
570
BID
Increase
633
BID
350-499
443
BID
Increase
507
BID
350-499
380
BID
Increase
443
BID
350-499
317
BID
Increase
380
BID
350-499
507
QD
Increase
570
QD
500-800
570
BID
No change
570
BID
500-800
443
BID
No change
443
BID
500-800
380
BID
No change
380
BID
500-800
317
BID
No change
317
BID
500-800
507
QD
No change
507
QD
>800
570
BID
Decrease
507
BID


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>800
443
BID
Decrease
380
BID
>800
380
BID
Decrease
317
BID
>800
317
BID
Decrease
253
BID
>800
507
QD
Decrease
380
QD
BID = twice-daily; QD = once-daily; TID = thrice-daily


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APPENDIX 3.
HYPOGONADAL QUALITY OF LIFE (QOL)
QUESTIONNAIRES
AMS Questionnaire
Which cl the fdlcNwng symptoms apply to you at thrs time? Please, mark the appropriate box for each
symptom Far symptoms that do not apply, please mark 'non?"
Symptoms:
extremely
mild
moderate severe severe
none
I
I
1
I
Score = 1
3
4
5
2
1
Decline in your feeling of general well-being
(general state of health, subjective feeling)
2.
Joint pain and muscular ache (lower back pain
joint pain, painn a tanb. general back acne)
.—,
3
Excessive sweating (unexpected'sudden episodes
of sweating, hot flushes independent of strain).—.,
4
Sleep problems (cftfficajlty in faikng asleep, diffictity
in sleeping through, waking up early and feeling tired
poor sleep. sleeplessness)
5.
Increased need for sleep, often feeling tired
..
6.
Irritability (feeling aggressive, easily upset about
little things, moody)__
____
——
_
7.
Nervousness (inner tension, restlessness, feeling fidgety) ...D
Q
B
Anxiety (feefing panicky)
6
Physical exhaustionIlacking vitality (general decrease
in performance, reduced activity, lacking interest CJ leisure
acdvaes, feeing of getting less done, of achieving less, of
having to force oneself to undertake activities).
10. Decrease in muscular strength (feeing of weakness) _—
11
Depressive mood (feeling down. sad. on the verge of tears
lack of drive, mood swings, feelingnothing rs of any use)—__
G
12. Feeling that you have passed your peak
13. Feeling burnt out, having hit rock-bottom
14
Decrease in beard growth
_—
15. Decrease in ability/frequency to perform sexually
10. Decrease in the number of morning erections
—O
17. Decrease in sexual desire/libido (lacking pleasure in sex.
lacking desire for sexual intercourse) ..
.ÿ
.ÿ
n
.ÿ
Have you got any other major symptoms?
If Yes. please describe:_
Yes
No
THANK YOU VERY MUCH FOR YOUR COOPERATION
' •i! *•!..
•
Vi'* 1 1
J; •••:' \>W
:
i •


TesoRx Pharma, LLC 
TSX-011 Dose Response Study
Protocol Number: TT-018
Confidential
Page 66
Male Sexual Dysfunction Multinational Survey of the Aging Male (MSAM-7; libido 
questions only)
The next questions askabout sexualdesire. Let'sdefinesexualdesire as afeeling thatmay
include wanting to haw a sexualexperience (e.g. masturbation or intercourse*), thinkingabout
sex, orfeelingfrustrateddue to lackofsex.
Q22. Over the past 4 weeks, how often have you felt sexual desire?
Pleaselick one box only.
Almost always or always
Most times (much more than half the time)
Sometimes (about half the time)
A few times (much less thanhalf the time)
Almost never or never
1
Q23. Over the past 4 weeks, how would you rate your level of sexual desire?
Please tick one box only.
Very high
High
Moderate
Low
.
.
Very low or none at all
S2
,y*3
..>4
SS


TesoRx Pharma, LLC 
TSX-011 Dose Response Study
Protocol Number: TT-018
Confidential
Page 67
Division ofEndocrinology, Harbor-UCLA Research andEducation Institute
Psychosexual Daily Questionnaire
(a) Center No.:
(b) Subject No.:
(c) Visit No.:
(d) Day:
(e) Date:
1. Please rate your overall level of sexual desire today by circling the appropriate number bebw:
0-1-2-3-4-5-6-{
venJlow
very hioh
none
2. Please rate highest level of enjoyment or pleasure of any sexual activity that you experienced today.
(a) without a partner (e.g., masturbationl sexual fantasies) and/or (b) with a partner (e.g., kissing, intercourse) by circling
the appropriate number bebw.
(a) Without a partner
0-1-2
3-4-5-6-7
none I
I very high enbvment/nleasure
0
1-2-3-4-5-6
7
(b) With a partner
I very high eniovment/pleasure
none
I
Iyes
(c) Please indicate if partner is available
3. Please rate your mood by writing the number that conesponds to the scale below. For each item 0 indicates that the descriptor
is not at all true; 7 indicates that the descriptor is very true for you today.
not at all true 0-1-2 --3-4-5
(d) Full of pep/energetic?_
(e) Sad or Blue?_
(f) Tired?_
6-7 very true
(g) Friendly?_
(h) Nervous?_
(i) Well/goodi.
(a) Angry? _
(b) Alert? _
(c) Irritable?_
4. For all of the items bebw check yes if you have experienced (or are experiencing) today, otherwise check no.
Yes
No
(a)
daydreams
(b)
(ÿanticipation of sex
I
I I
lsexual interactions
— — with partner
(d)
|
[flirting (by you)
Yes
No
(e)
|
[orgasm
/A I
I I
(flirting (by others
— —Toward you)
(g) (ÿ
(h)
|
[intercourse
Yes No
(i) [ÿ
(j)
spontaneous erection
(k)
spontaneous erection
I
I I
lerection in response
— —no sexual activity
Answer the following two questions only if you experienced an erection as shown in No. 4. i-l above.
5. If you experienced an erection today, indicate the % full erection that you experienced by circling the appropriate number below
(make a reasonable estimate):
%=
0
10
20
30
40
50
60
70
80
90
100
6. If you experienced an erection today, indicate whether it was maintained for a satisfactory duration by circling the appropriate
number below:
not satisfactory 0-1-2-3 —4-5-6-7 very satisfactory
Day is the relative day of the reporting period/week (i.e., 1,2,3,4,5,6, or 7)

SAP_001.pdf: 
PAREXEL International 
Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
Page 1 of 84 
 
 
STATISTICAL ANALYSIS PLAN 
 
 
 
Protocol TT-018 
 
 
 
 
 
A Phase 1/2a Study to Determine the Dose Response 
Pharmacokinetics of TSX-011 (Testosterone Undecanoate)  
in Hypogonadal Males 
 
 
 
 
PAREXEL Study Number 235004 
 
 
 
Version: Final 1.0 
Date:  13 June 2018 
 
 
 
 
 






PAREXEL International 
Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
Page 4 of 84 
 
 
TABLE OF CONTENTS 
SIGNATURE PAGE – TESORX PHARMA ................................................................................. 2 
SIGNATURE PAGE - PAREXEL ................................................................................................. 3 
TABLE OF CONTENTS ................................................................................................................ 4 
1. 
STATISTICAL ANALYSIS PLAN .................................................................................. 9 
2. 
STUDY OBJECTIVES AND HYPOTHESES PER PROTOCOL ................................... 9 
2.1 
PRIMARY OBJECTIVES ................................................................................................ 9 
2.2 
SECONDARY OBJECTIVES .......................................................................................... 9 
2.3 
EXPLORATORY OBJECTIVES ..................................................................................... 9 
3. 
STUDY DESIGN PER PROTOCOL .............................................................................. 10 
3.1 
STUDY ENDPOINTS PER PROTOCOL ...................................................................... 12 
3.2 
STUDY POPULATION .................................................................................................. 13 
3.3 
SAMPLE SIZE ................................................................................................................ 13 
3.4 
RANDOMIZATION AND BLINDING ......................................................................... 13 
3.5 
DOSE ADMINISTRATION ........................................................................................... 13 
3.5.1 
ADAPTIVE DESIGN CRITERIA .................................................................................. 15 
3.5.1.1 DOSE ADJUSTMENT PERIOD 3 DAY 16................................................................... 15 
3.5.1.2 DOSE ADJUSTMENT PERIOD 3 DAY 26................................................................... 16 
3.6 
MEAL ADMINISTRATION .......................................................................................... 18 
3.7 
INTERIM ANALYSIS .................................................................................................... 19 
4. 
PAREXEL STUDY ANALYSIS VARIABLES ............................................................. 19 
4.1 
DEMOGRAPHIC AND BACKGROUND VARIABLES .............................................. 19 
4.2 
SAFETY VARIABLES ................................................................................................... 19 
4.2.1 
ADVERSE EVENTS ...................................................................................................... 19 
4.2.2 
CLINICAL LABORATORY TESTS ............................................................................. 19 
4.2.2.1 OTHER LAB ASSESSMENTS - TESTOSTERONE LEVELS, PSA ........................... 21 
4.2.3 
VITAL SIGNS ................................................................................................................. 21 
4.2.4 
ELECTROCARDIOGRAMS .......................................................................................... 22 
4.2.5 
PHYSICAL EXAMINATION ........................................................................................ 22 
4.2.6 
CONCOMITANT MEDICATIONS ............................................................................... 22 
4.3 
QUALITY OF LIFE ASSESSMENTS ........................................................................... 23 
4.4 
PHARMACOKINETIC VARIABLES ........................................................................... 23 
4.4.1 
PHARMACOKINETIC PARAMETER CALCULATION METHODS ........................ 25 


PAREXEL International 
Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
Page 5 of 84 
 
 
4.5 
PHARMACODYNAMIC VARIABLES ........................................................................ 25 
4.6 
EFFICACY VARIABLES .............................................................................................. 25 
4.7 
ANALYSIS POPULATIONS ......................................................................................... 25 
4.7.1 
SAFETY POPULATION ................................................................................................ 25 
4.7.2 
PHARMACOKINETIC POPULATION (PK) ................................................................ 25 
5. 
STATISTICAL REPORTING ........................................................................................ 26 
5.1 
GENERAL CONSIDERATIONS FOR DATA PRESENTATIONS ............................. 26 
5.2 
TREATMENT IDENTIFICATION ................................................................................ 27 
6. 
SUBJECT AND TREATMENT INFORMATION......................................................... 27 
6.1 
SUBJECT DISPOSITION ............................................................................................... 27 
6.2 
ELIGIBILITY CRITERIA AND PROTOCOL DEVIATIONS ..................................... 28 
6.3 
EXCLUSION TESTS ...................................................................................................... 28 
6.4 
DEMOGRAPHIC DATA ................................................................................................ 28 
6.5 
MEDICAL HISTORY ..................................................................................................... 28 
6.6 
CONCOMITANT MEDICATION ................................................................................. 28 
6.7 
DOSE ADMINISTRATION ........................................................................................... 28 
7. 
PHARMACOKINETIC CONCENTRATIONS AND PARAMETERS ........................ 29 
7.1 
PLASMA CONCENTRATIONS .................................................................................... 29 
8. 
SAFETY ANALYSIS ..................................................................................................... 29 
8.1 
ADVERSE EVENTS ...................................................................................................... 29 
8.2 
CLINICAL SAFETY LABORATORY TESTS (HEMATOLOGY, 
CHEMISTRY, URINALYSIS) ....................................................................................... 31 
8.2.1 
HEMATOLOGY AND CHEMISTRY ........................................................................... 31 
8.2.2 
URINALYSIS ................................................................................................................. 31 
8.2.3 
LABORATORY COMMENTS ...................................................................................... 32 
8.2.4 
OTHER LABORATORY ASSESSMENTS ................................................................... 32 
8.3 
VITAL SIGNS ................................................................................................................. 32 
8.4 
12-LEAD SAFETY ECG ................................................................................................ 32 
8.5 
PHYSICAL EXAMINATION ........................................................................................ 33 
8.6 
IPSS QUESTIONNAIRE ................................................................................................ 33 
8.7 
QOL QUESTIONNAIRE ................................................................................................ 33 
9. 
REPORTING OUTPUT .................................................................................................. 34 
10. 
REFERENCES ................................................................................................................ 34 
11. 
SUMMARY TABLES .................................................................................................... 35 
12. 
LISTINGS........................................................................................................................ 36 


PAREXEL International 
Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
Page 6 of 84 
 
 
13. 
TABLE SHELLS ............................................................................................................. 37 
14. 
LISTING SHELLS .......................................................................................................... 56 
 


PAREXEL International 
Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
Page 7 of 84 
 
 
Abbreviations and Definitions 
AE 
Adverse event 
ALT 
L-alanine aminotransferase 
AST 
L-aspartate aminotransferase 
AUC 
Area under the curve 
AUClast 
Area under the concentration versus time curve from time 0 to the last 
measurable concentration 
AUCt 
Area under the concentration versus time curve, from time 0 to the last 
measurable concentration on or before time t 
AUCinf 
Area under the concentration versus time curve from time 0 to infinity 
BLQ 
Below the lower limit of quantification 
BMI 
Body Mass Index 
BUN 
Blood urea nitrogen 
Cavg,ss 
Steady-state average drug concentration 
CI 
Confidence interval 
CL/F 
Apparent total body clearance after oral dosing 
CS 
Clinically significant 
Cmax 
Maximum plasma TSX-011 concentration determined directly from the 
concentration-time profile 
Cmin 
Minimum drug concentration 
CV 
Coefficient of variation 
CYP 
Cytochrome P450 
DHT 
Dihydrotestosterone 
DHTU 
Dihydrotestosterone undecanoate 
ECG 
Electrocardiogram 
HBsAg 
Hepatitis B surface antigen 
HIV 
Human immunodeficiency virus 
IMP 
Investigational Medicinal Product 
Lambda z 
Apparent elimination rate constant 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCS 
Not clinically significant 
PDQ 
Psychosexual Daily Questionnaire 
PK 
Pharmacokinetic 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
Standard deviation  
SOC 
System Organ Class 
t½ 
Apparent elimination half-life 
TEAE 
Treatment-emergent adverse event 
Tmax 
Time of the maximum measured concentration over the specified 
interval. If the maximum value occurs at more than one time point, Tmax 
is defined as the first time point with this value. 
Tmin 
Time of the minimum measured concentration over the specified interval 


PAREXEL International 
Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
Page 8 of 84 
 
 
TU 
Testosterone undecanoate 
Vss/F 
Volume of distribution at steady state after oral dosing 
WHO 
World Health Organization 
 
 


PAREXEL International 
Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
Page 9 of 84 
 
 
 
1. 
Statistical Analysis Plan 
This Statistical Analysis Plan (SAP) is based on the final protocol TT-018 dated 31 
July 2017 and incorporates protocol Version 2.0 dated 26 October 2017 and Version 
3.0. dated 05 March 2018. The SAP provides details on the planned statistical 
methodology for analysis of the study data.  The SAP also outlines the statistical 
programming specifications for the tables, listings and figures.  It describes the safety, 
pharmacokinetic (PK) variables, the anticipated data transformations and 
manipulations, and other details of the analyses not provided in the study protocol.  
This SAP covers the planned analysis of all data collected electronically in Clinbase 
and provided by external vendors. 
2. 
Study Objectives and Hypotheses per Protocol 
2.1 
Primary Objectives 
To assess the pharmacokinetics (PK) of total testosterone after oral dosing of TSX-
011 in hypogonadal adult male subjects following: 1) single ascending doses, and 2) 
single or multiple daily doses administered over a 30-day period in a fixed-dose and 
dose-adjustment adaptive design. 
2.2 
Secondary Objectives 
 To assess the safety and tolerability of TSX-011 in hypogonadal adult male 
subjects by evaluating treatment-emergent adverse events (TEAEs). 
 
 To assess the PK of free testosterone, testosterone undecanoate (TU), 
dihydrotestosterone (DHT), and dihydrotestosterone undecanoate (DHTU) 
after oral dosing of TSX-011 in hypogonadal adult male subjects following: 1) 
single ascending doses, and 2) single or multiple daily doses administered over 
a 30-day period in a fixed-dose and dose-adjustment adaptive design. 
2.3 
Exploratory Objectives 
 To assess the effect of TSX-011 on hypogonadal symptoms as measured by 
hypogonadal quality of life (QOL) questionnaires: Aging Male Symptom 
(AMS) scale, Multinational Survey of the Aging Male-7 (MSAM-7; libido 
questions only), and Psychosexual Daily Questionnaire (PDQ).  
 


PAREXEL International 
Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
Page 10 of 84 
 
 
 To determine the preferred method of PK specimen collection - Serum or 
enzyme inhibited plasma. 
3. 
Study Design per Protocol 
The study will be conducted as an open-label 3-period investigation as follows: 
 
 Period 1. Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 
380 mg TSX-011 (fed), and 570 mg TSX-011 (fed).  
 
 Period 2. 380 mg TSX-011 twice daily dosing period of 15 days in fed 
conditions. 
 
 Period 3. Dose-adjusted adaptive design period: TSX-011 dose adjustment 
permitted on Day 16 and Day 26 based on 6 hours postdose (± 15 minutes) 
testosterone level on Day 8 and Day 19, respectively; dosing period of 15 
days. 
 
Dosing amounts of TSX-011 in this protocol refer to TU amounts. 
 
Up to 24 subjects will be enrolled in this study to yield 16 evaluable subjects, and it is 
desired that the same 24 subjects participate in all 3 study periods.  
 
The three initial cohorts of 3 subjects each will complete Periods 1, 2, and 3 prior to 
enrolment of remaining subjects. Interim review of safety and efficacy of TSX-011 
will occur prior to enrolment of remaining subjects in the study. Dose response and 
optimum dosing conditions and PK specimen collection methods (serum vs. enzyme 
inhibited plasma) will be confirmed prior to remaining subject enrolment.  
 
Enrolment will be managed to result in at least 10 evaluable native Japanese 
subjects. Subjects may be replaced at the discretion of the Sponsor in 
consultation with the Principal Investigator (PI). 
 
A schematic of the study design is given in the below figure:


PAREXEL International 
Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
Page 11 of 84 
 
 
Study Design for Study TT-018 
 
 
 
 


PAREXEL International 
Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
Page 12 of 84 
 
 
3.1 
Study Endpoints per Protocol 
The primary endpoints of the study are PK parameters for testosterone after TSX-
011 administration under fed (or fasted [Period 1, 190 mg dose only]) conditions 
as described below: 
1. Period 1 (ascending single doses): 
a. Total (actual measured) testosterone, AUCt, Cmax, Tmax, Cmin, 
Tmin, and Cmax to Cmin ratio. 
b. Baseline-corrected (BC) testosterone: z, t1/2, CL/F, Vss/F, Cmax, 
AUClast, and AUC∞. 
2. Period 2 (twice-daily dosing) Days 1 and 15 and Period 3 (dose-
adjustment adaptive design) Day 30: 
a. Total testosterone: AUCt, Css,avg, Cmax, Tmax, Cmin, Tmin, and Cmax 
to Cmin ratio. 
 
The secondary endpoints of the study are as follows: 
 
1. Number and severity of TEAEs and results of physical examinations, 
electrocardiograms (ECGs), vital sign measurements, and clinical laboratory 
tests (serum chemistry, hematology, and urinalysis) following a single dose of 
TSX-011 and following a single- or multiple-daily dose regimen of TSX-011 
using a fixed-dose or a dose-adjustment adaptive design. 
 
2. PK parameters (AUCt, Cmax, Tmax, Cmin, and Cavg) for free testosterone, 
TU, DHT, and DHTU under fed (or fasted [Period 1, 190 mg dose only]) 
conditions following: 1) ascending single doses of TSX-011, and 2) single- or 
multiple-daily dose regimen of TSX-011 using a fixed-dose and dose-
adjustment adaptive design. 
The exploratory endpoints of the study are as follows: 
1. Hypogonadal symptoms as measured by the hypogonadal QOL 
questionnaires: AMS scale, MSAM-7 (libido questions only), and 
PDQ. 
2. Duplicate PK analysis (serum and enzyme inhibited plasma) in the first 
9 subjects enrolled. 
 


PAREXEL International 
Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
Page 13 of 84 
 
 
3.2 
Study Population 
The study population will consist of hypogonadal adult male subjects18 to 75 years of 
age at time of study enrolment.  Subjects must be able to provide written informed 
consent and meet all the inclusion criteria and none of the exclusion criteria as stated 
in the protocol. 
 
Hypogonadal males are those with at least 1 serum testosterone level <350 ng/dL, 
10 am [± 2 hour] sample taken during the screening period. 
3.3 
Sample Size 
The study is a proof-of-concept study with adaptive dosing. The sample size chosen 
for this study was selected without statistical considerations but has been determined 
adequate to meet the study objectives. 
3.4 
Randomization and Blinding 
This is a non-randomized study. All subjects will be exposed to the same set of 
treatment administrations and will be dosed in all periods using non-random 
assignment to treatment. 
 
If Period 2 Day 8 (6 hours postdose ± 15 minutes) total testosterone is >800 ng/dL, 
subjects will be assigned by non-random assignment in a 1:1 ratio to receive: 
 
 Schedule A: 317 mg (TU) TSX-011 twice daily OR 
 Schedule B: 507 mg (TU) TSX-011 once daily 
 
Period 2 subjects will be stratified during treatment assignment per their 
Japanese/non-Japanese classification.  
 
Overall enrolment will be managed to result in at least 10 evaluable Japanese subjects.  
 
All treatment assignments for all periods of dosing will be managed within the 
electronic data capture system. The study is an open-label study, and as such, no 
blinding will be performed. 
 
3.5 
Dose Administration 
The investigational product is TSX-011.  
 
TSX-011 capsule(s) will be administered orally with at least 240 mL of water.  


PAREXEL International 
Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
Page 14 of 84 
 
 
Dosing (swallowing capsules) should be completed within 5 minutes of starting. All 
drug administration procedures will be performed at the clinical study unit during 
confinement. The actual time of each dose administration will be recorded to the 
nearest minute, and this will be used in conjunction with the actual 
sample times to determine PK parameters as appropriate. 
 
 
 
 
Period 1 
 
This is conducted as an ascending single-dose study of TSX-011 at 3 doses, with the 
lowest dose administered under fed and fasted conditions: 190 mg TSX-011 in the fed 
state, 190 mg TSX-011 in the fasted state, 380 mg TSX-011 in the fed state, and 570 
mg TSX-011in the fed state. Before exposure to TSX-011, a 24-hour baseline 
measurement of testosterone and DHT will be performed for each subject. Samples 
for analysis of testosterone will be obtained at the following time points on Day -1: 
hour 0 (8 am ± 60 minutes) and 1.5, 3, 4.5, 6, 8, 12, 16, and 24 hours (± 15 minutes 
for each time point). Day -1 is during screening (prior to initial dose).  Day -1 
endogenous blood samples are taken to establish pre-dosing T levels.  
 
The day following the sampling for endogenous testosterone (Day 1) in Period 1, each 
subject will receive the first single dose of TSX-011 (190 mg) under fed conditions. 
Following administration of TSX-011, blood samples will be obtained over a 24-hour 
period for PK analysis. Subjects will undergo a minimum 3-day and up to 7-day 
washout period between each of the doses of TSX-011 in Period 1. After the 570 mg 
TSX-011 dose in Period 1, a minimum 3-day and up to 7-day (14 day for three initial 
3 subject cohorts) washout period will occur before the start of Period 2. 
 
Period 2 
 
Subjects in a fed state will receive 380 mg TSX-011 twice daily (8 am ± 60 minutes 
and 6 pm ± 60 minutes) for 15 days (Days 1 through 15). Pharmacokinetic 
assessments over 24 hours will occur on Days 1 and 15. On Day 8 in Period 2, before 
the morning dose, a trough PK blood sample will be drawn. In addition, on Day 8, 6 
hours (± 15 minutes) after the morning dose, testosterone levels will be obtained and 
used to dose adjust according to the adaptive dosing design described below.  The 
TSX-011 dose will be adjusted up or down beginning with the Day 16 (Period 3) 
morning dose, based on established dosing rules described below. 
Period 3 
Period 3 is a dose-adjusted adaptive design period that begins on Day 16, with the 
first adjusted TSX-011 dose administered in the fed state on a once-daily or twice-
daily schedule. The 6-hour postdose (± 15 minutes) testosterone level on Day 19 will 


PAREXEL International 
Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
Page 15 of 84 
 
 
be used to perform the second and final TSX-011 dose adjustment, based on 
established criteria.  
As specified by the dose adjustment rules below, Day 26 begins with either a once-
daily, twice-daily, or thrice-daily fed dose schedule. The thrice-daily dose schedule 
will be administered only to non-responders (Cavg testosterone <350 ng/dL despite 1 
dose adjustment). On Day 30, a 24-hour PK assessment will be performed, and the 
subject’s participation in the study is completed the morning of Day 31. 
 
3.5.1 Adaptive Design Criteria 
3.5.1.1 
Dose Adjustment Period 3 Day 16 
 If Period 2 Day 8 (6 hours postdose ± 15 minutes) total testosterone is <350 
ng/dL, adjust the first dose of Period 3 (Day 16 dose) to 570 mg (TU) TSX-
011 twice daily. 
 
 If Period 2 Day 8 (6 hours postdose ± 15 minutes) total testosterone is ≥350 
ng/dL and <500 ng/dL, adjust the first dose of Period 3 (Day 16 dose) to 443 
mg (TU) TSX-011 twice daily. 
 
 If Period 2 Day 8 (6 hours postdose ± 15 minutes) total testosterone is 500 to 
800 ng/dL, inclusive, maintain first dose of Period 3 (Day 16 dose) at 380 mg 
(TU) TSX-011 twice daily. 
 
 If Period 2 Day 8 (6 hours postdose ± 15 minutes) total testosterone is >800 
ng/dL, the first dose in Period 3 (Day 16 dose) will be by manual assignment  
in a 1:1 ratio to receive either: 
o Schedule A: 317 mg (TU) TSX-011 twice daily OR 
o Schedule B: 507 mg (TU) TSX-011 once daily. 
In this case subjects will be stratified during treatment assignment per their 
Japanese/non-Japanese ethnicity. All study subjects will be manually assigned to 
schedule A or B to ensure a balanced dosing schedule. 
 
 
 
 
 


PAREXEL International 
Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
Page 16 of 84 
 
 
Table 1: 
Adaptive Design and Dose Adjustment Criteria 
Period 2 - Days 1 to 15 
Period 3 - Dose Adjustment on Day 16 
Day 8 T level 
(ng/dL) 
Starting  
Dose (mg) 
 
Frequency 
 
Dose Change 
New Dose 
(mg) 
 
Frequency 
<350 
380 
BID 
Increase 
570 
BID 
350-499 
380 
BID 
Increase 
443 
BID 
500-800 
380 
BID 
No change 
380 
BID 
>800 
380 
BID 
Decrease 
(treatment assignment 1:1) 
317 
BID 
>800 
380 
BID 
Decrease 
(treatment assignment 1:1) 
507 
QD 
 
 
3.5.1.2 
Dose Adjustment Period 3 Day 26 
 
 If Period 3 Day 19 (6 hours postdose ± 15 minutes) total testosterone is 
<350 ng/dL, dose adjust subjects to 570 mg TU dosing thrice daily for their 
Day 26 dose. Dosing times should be (8 am ± 60 minutes, 8 hours post 
morning dose ± 15 minutes, and 14 hours post morning dose ± 15 minutes). 
 
 If Period 3 Day 19 (6 hours postdose ± 15 minutes) total testosterone is ≥350 
ng/dL and <500 ng/dL, then their Day 26 dose will be as follows: 
a. Dose adjust subjects on once-daily dosing from 507 mg TU daily to 
570 mg TU daily. 
b. Dose adjust subjects on twice daily dosing as follows: 
o If dose is 570 mg TU twice daily, increase to 633 mg TU twice 
daily. 
o If dose is 443 mg TU twice daily, increase to 507 mg TU twice 
daily. 
o If dose is 380 mg TU twice daily, increase to 443 mg TU twice 
daily. 
o If dose is 317 mg TU twice daily, increase to 380 mg TU twice 
daily. 


PAREXEL International 
Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
Page 17 of 84 
 
 
 If period 3 Day 19 (6 hours post-dose ± 15 minutes) total testosterone is 
between 500 and 800 ng/dL inclusive, continue the current dose for their Day 
26 dose. 
 
 If Period 3 Day 19 (6 hours postdose ± 15 minutes) total testosterone is >800 
ng/dL, their Day 26 dose should be decreased as follows: 
a. For once-daily dosing subjects change the dose from 507 
mg TU daily to 380 mg TU daily. 
b. For the twice-daily dosing group: 
o If dose is 570 mg TU twice daily, decrease to 507 mg TU twice 
daily. 
o If dose is 443 mg TU twice daily, decrease to 380 mg TU twice 
daily. 
o If dose is 380 mg TU twice daily, decrease to 317 mg TU twice 
daily. 
o If dose is 317 mg TU twice daily, decrease to 253 mg TU twice 
daily. 
 


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Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
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 Table 2: 
Adaptive Design and Dose Adjustment Criteria 
Period 3 - Day 16 to 30 
Period 3 - Dose Adjustment on Day 26 
 
Day 19 T level 
(ng/dL) 
Starting  
Dose 
(mg) 
 
 
Frequency 
 
 
Dose Change 
 
New Dose 
(mg) 
 
 
Frequency 
<350 
all 
 
Increase 
570 
TID 
350-499 
570 
BID 
Increase 
633 
BID 
350-499 
443 
BID 
Increase 
507 
BID 
350-499 
380 
BID 
Increase 
443 
BID 
350-499 
317 
BID 
Increase 
380 
BID 
350-499 
507 
QD 
Increase 
570 
QD 
 
 
 
 
 
 
500-800 
570 
BID 
No change 
570 
BID 
500-800 
443 
BID 
No change 
443 
BID 
500-800 
380 
BID 
No change 
380 
BID 
500-800 
317 
BID 
No change 
317 
BID 
500-800 
507 
QD 
No change 
507 
QD 
>800 
570 
BID 
Decrease 
507 
BID 
>800 
443 
BID 
Decrease 
380 
BID 
>800 
380 
BID 
Decrease 
317 
BID 
>800 
317 
BID 
Decrease 
253 
BID 
>800 
507 
QD 
Decrease 
380 
QD 
BID = twice daily; QD = once daily; TID = thrice daily 
 
3.6 
Meal Administration 
 
Meals and/or snacks will be provided as appropriate (breakfast, lunch, and dinner) on 
predose days (e.g., Day -1); thereafter, the meal schedule will be as described in the 
protocol section 13.7. 
 
 


PAREXEL International 
Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
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3.7 
Interim Analysis 
Three starting cohorts of 3 subjects each will complete Periods 1, 2, and 3 prior to 
enrolment of the remaining subjects. For purpose of this protocol ‘enrolment’ is the 
subject first dose (i.e., 190 mg fed Day 1). An interim review of TSX-011 safety and 
efficacy data (including PK data) will occur prior to enrolling the remaining subjects 
in the study. Any subject in these cohorts who fails to complete all 3 study periods or 
is determined to be a non-responder will be replaced.  
4. 
PAREXEL Study Analysis Variables 
4.1 
Demographic and Background Variables 
The following demographic and anthropometric information will be recorded: 
 Date of informed consent 
 Medical history (including previous and current medical conditions and 
medications) 
 Drug, alcohol, smoking and caffeine use (previous history and current) 
 Age calculated as (date of informed consent – date of birth)/365.25 
 Gender 
 Ethnic origin 
 Race 
 Height (cm) 
 Body weight (kg) 
 Body mass index (BMI) (kg/m2) 
4.2 
Safety Variables 
4.2.1 Adverse Events 
Adverse event (AE) monitoring will occur from the time consent is obtained until the 
end of the subject’s participation in the study (i.e., the subject has discontinued or 
completed the study). 
4.2.2 Clinical Laboratory Tests 
Laboratory safety tests for chemistry, hematology and urinalysis will be performed at 
the following time points: 
Period 1: Screening, Day-1, and Day 2; Period 2: Day 2, Day 8, Day 16; Period 3: 
Day 31. 


PAREXEL International 
Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
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The following safety laboratory parameters will be measured: 
Serum Chemistry 
 Albumin 
 Alkaline phosphatase 
 AST 
 ALT 
 Blood urea nitrogen 
 Creatinine 
 Creatine kinase  
 Lactate dehydrogenase 
 Glucose 
 Bilirubin (total)* 
 Total protein 
 Sodium 
 Potassium 
 Calcium 
 Chloride 
 Total cholesterol 
 Triglycerides 
 Uric acid 
 High-density lipoprotein (HDL) 
 Low-density lipoprotein (LDL) 
 
Hematology  
 
 Hemoglobin 
 Hematocrit 
 Total and differential leukocyte count 
 Red blood cell count 
 Platelet count 
 White blood cell count 
 HbA1c** 
 
Urinalysis 
 pH 
 Specific gravity 
 Protein 
 Glucose 
 Ketones 
 Nitrite 
 Bilirubin 


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Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
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 Blood 
 Urobilinogen 
 Leukocyte esterase 
 Microscopic assessment for cells and casts 
 
Microscopic urinalysis will be performed if urinalysis results are abnormal.  
 
Virology 
 
HIV test** 
 
Hepatitis B surface antigen** 
 
Hepatitis C virus** 
Urine drug screen *** 
 
Cocaine 
 
Cannabinoids 
 
Alcohol 
 
Opiates 
 
Barbiturates 
 
Amphetamines 
 
Benzodiazepines 
 
 
If total bilirubin results are above the upper limits of normal, direct and indirect  
bilirubin analysis will be performed. 
** To be performed at screening only. 
*** To be performed at screening and at each confinement check-in. 
 
After screening, safety laboratory tests will be performed in the fasted state (at least 8  
hours fasted). 
 
4.2.2.1 
Other Lab Assessments - Testosterone Levels, PSA 
Testosterone levels will be collected at the following times for each treatment period: 
 
Period 1: screening; Day 1, 6 hours post 
Period 2: Day 8, 6 hours post 
Period 3: Day 19 
 
PSA values will be assessed at screening period 1, Day 31 period 3 
4.2.3 Vital Signs 
Vital signs will be measured and assessed at the following times: 
Period 1: Screening, Day-1, on Day 1 at time 0, 6 hours post, 24 hours post; 


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Protocol Number TT-018 
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13 June 2018 
 
 
 
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Period 2: Day -1, Day 1 at 0 hour, 8 hours post, 16 hours post; Day 2, Day 8, Day 14, 
Day 15 at 0 hour, 8 hours post, 16 hours post. 
Period 3:  Day 16, Day 29, Day 31. 
 
The following vital signs will be measured:  
 
 Blood pressure (systolic and diastolic [mmHg]);  
 Pulse (beats per minute [bpm]);  
 Oral body temperature (°C);  
 Respiratory rate (breaths per minute).  
 
All vital sign measurements will be single measurements. 
4.2.4 Electrocardiograms 
The 12-lead ECGs will be performed at the following times: 
Period 1: Screening, Day-1, on Day 2; 
Period 2: Day 2, Day 8. 
Period 3:  Day 16, Day 31. 
 
The following ECG parameters will be collected: PR interval, QRS interval, RR 
interval, QT interval, and QTc interval (QTcB and QTcF). 
 
The ECG will be evaluated by the Investigator as ‘Normal’, ‘Abnormal, NCS’ or 
‘Abnormal, CS’. 
4.2.5 Physical Examination 
Physical examinations will be performed at the following times for each period: 
 
Period 1: Screening, Day –1, Day 2; 
Period 2: Day -1, Day 14; 
Period 3:  Day 16, Day 29, Day 31. 
4.2.6 Concomitant Medications 
Concomitant medication use will be recorded for the 30 days prior to Screening until 
the final discharge visit (i.e., end of the study). 


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Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
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4.3 
Quality of Life Assessments 
Measurements of QOL related to hypogonadal symptoms will be assessed at the 
following time points: Screening; Period 2: Day -1, Day 15;  Period 3: Day 19, 
Day 31. QOL will be assessed by applying the following questionnaires:  
 International Prostrate Symptom Score (IPSS) 
 AMS scale 
 Male Sexual Dysfunction Multinational Survey of the Aging male 
(MSAM-7, libido questions only) 
 Psychosexual Daily Questionnaire (PDQ) 
 
4.4 
Pharmacokinetic Variables 
Period 1: Blood samples for the determination of endogenous testosterone and DHT 
will be collected for a single 24-hour period before any study subject exposure to 
TSX-011. This baseline assessment of endogenous testosterone and DHT will be 
assessed over a 24-hour predose interval (Day -1) at 0, 1.5, 3, 4.5, 6, 8, 12, 16, and 24 
hours. 
 
Blood samples for 24-hour post-dosing will be collected on Day 1 of each dosing PK 
(190, 380, 570 mg TU) at 0, 1.5, 3, 4.5, 6, 8, 12, 16, and 24 hours. 
 
 
Period 2: Blood samples for determination of PK measurements will be collected at 0, 
1.5, 3, 4.5, 6, 8, 10, 11.5, 13, 14.5, 16, 18, and 24 hours on Day 1 and Day 15. The 
three initial cohorts of 3 subjects each will have additional PK samples taken. 
Specifically, duplicate PK samples (one serum and one plasma) will be taken on Day 8 
prior to dosing and at 6 hours (± 15 minutes) after the morning dose. 
 
The plasma sample values will be used to dose adjust according to the adaptive dosing 
design. 
 
For the first cohort, if TU is detectable at a level 5 times above the LLOQ (i.e. 10 
ng/ml) in the previously collected Day 8 samples, then for PK assessments on Day 
15, all blood samples will be collected in duplicate (one serum and one plasma). 
For the second and third cohorts, Day 15 samples will be collected in duplicate. 
The serum sample shall be processed initially, and only if TU is detectable at a 
level 5 times above the LLOQ (i.e. 10 ng/ml) shall the enzyme inhibited plasma 
sample undergo PK analysis. 


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TesoRx Pharma, LLC 
Protocol Number TT-018 
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Period 3: On Day 30, PK samples for a 24-hour PK profile will be obtained at the 
following sampling times based upon the daily dosing regimen. 
For subjects on once daily dosing, blood samples for determination of PK 
measurements will be collected at 0, 1.5, 3, 4.5, 6, 8, 12, 16, and 24 hours.  
 
For subjects on twice daily dosing, blood samples for determination of PK 
measurements (4-6 mL blood per time point) will be collected at 0, 1.5, 3, 4.5, 6, 8, 
10, 11.5, 13, 14.5, 16, 18, and 24 hours. 
 
For subjects on thrice daily dosing, blood samples for PK determination will be 
collected at 0, 1.5, 3, 4.5, 6, 8, 9.5, 11, 12.5, 14, 15.5, 17, 18.5, 20, and 24 hours. 
 
The three initial cohorts of 3 subjects each will have additional PK samples taken. 
Specifically, duplicate PK samples (one serum and one plasma) will be taken on Day 
19 at 6 hours (± 15 minutes) after the morning dose. The plasma sample values will 
be used to dose titrate according to the adaptive dosing design. 
 
PK Parameters 
 
Derivation of all PK parameters will be the responsibility of the sponsor. 
 
The following PK parameters will be calculated using both actual testosterone 
concentrations following dose administration of TSX-011: 
AUC12: 
The area under the concentration versus time curve, from time 0 to 
the last measurable concentration on or before time 12 hours, as 
calculated by a linear trapezoidal method. 
AUC24: 
The area under the concentration versus time curve, from time 0 to 
the last measurable concentration on or before time 24 hours, as 
calculated by a linear trapezoidal method. 
Cmax: 
Maximum measured concentration over the time span specified. 
Cavg: 
Average measured concentration over the time span specified. 
Cmin: 
Minimum measured concentration over the time span specified. 
Tmax: 
Time of the maximum measured concentration. If the maximum 
value occurs at more than one time point, Tmax is defined as the 
first time point with this value. 
Tmin: 
Time of the minimum measured concentration.  
 


PAREXEL International 
Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
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Table 2: Pharmacokinetic Parameters 
Parameter 
Definition 
Method of Determination 
Cmax 
Maximum plasma TSX-011 
concentration  
Taken directly from bioanalytical 
data 
Tmax 
The time to reach Cmax 
Taken directly from merged 
clinical and bioanalytical data, 
with time presented as actual 
elapsed time relative to dose 
 
4.4.1 Pharmacokinetic Parameter Calculation Methods 
PK parameters will be calculated by non-compartmental analysis methods from the 
concentration-time data following these guidelines: 
 Actual sampling times relative to dosing rather than nominal times will be 
used in the calculation of all derived PK parameters. 
 There will be no imputation of missing data.  
4.5 
Pharmacodynamic Variables 
Not applicable 
4.6 
Efficacy Variables 
Not applicable 
4.7 
Analysis Populations 
4.7.1 Safety Population 
 
The Safety population is defined as all randomized subjects who received at least  
one dose of study drug and have at least one post-baseline safety assessment. 
Subjects will be included in the analysis according to IP received. 
4.7.2 Pharmacokinetic Population (PK) 
The PK population is defined as all randomized subjects for whom at least one PK 
parameter of interest can be calculated. In general, on a parameter-by-parameter basis, 


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Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
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an individual subject’s data may be excluded from analysis if insufficient data are 
available for that subject to calculate the specific parameter in question. 
5. 
STATISTICAL REPORTING 
For the purposes of this SAP IP refers to any dose amount of study drug TSX-011. 
5.1 
General Considerations for Data Presentations 
Data for all enrolled subjects will be presented in the data listings.     
 
A subject who is enrolled but does not receive IP will be included in those data 
listings for which they have data but will be excluded from all data summaries. Data 
summaries will only include those subjects that receive IP.  
 
For those listings or data summaries where baseline and change from baseline 
measurements will be presented, unless stated otherwise the last observed 
measurement prior to the first dose of IP in a given period will be considered the 
baseline measurement for the post-dose assessments in that period.  
 
All pre- and post-dose assessments, including unscheduled assessments and repeats, 
will be included in the data listings. For unscheduled (repeat) assessments collected 
pre-dose, the last assessment taken for a time point will be used in the data summaries 
(summary tables, figures, and statistical analysis); for all post-dose time points, the 
original assessment for any given time point will be used in the data summaries 
(summary tables, figures, and statistical analysis). 
 
For data summaries of continuous variables will be summarized using descriptive 
statistics including: number of observations (n), mean (arithmetic and/or geometric), 
median, standard deviation (SD), minimum, and maximum. Frequencies and 
percentages will be used for summarizing discrete (categorical) data. In summaries for 
safety the denominator for all percents will be the number of subjects in a given 
treatment group.  
 
Data that are reported as missing will be excluded from all descriptive and non-
descriptive data analysis. There will be no imputation of data.  Observations that 
might be considered spurious (extreme relative to the majority of the data) will not be 
altered or removed from any presentation of the data, including the calculation of 
summary statistics (means, medians, etc.), unless approved by the sponsor.  
 
For data listings, all raw data will be reported/displayed exactly as provided. For 
summaries of quantitative safety data, the minimum and maximum value will be 
reported exactly as the raw data are reported; measures of central tendency (means, 


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Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
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medians) will be reported to one more decimal place than the raw data; measures of 
variance (SD) will be reported to two more decimal places than the raw data.   
Methods for summarizing PK data are described in section 7 of this SAP. 
 
Listings will include all subjects and will be sorted by subject number and time point 
(where applicable). All derived data used in a data summary or statistical analysis will 
be listed.  All data listings will include a column for treatment period and subject 
number.  
5.2 
Treatment Identification  
The following will be used to identify the treatment in applicable data listings, tables 
and figures: 
Period 1 Treatment 
 
 190 mg TSX-011, Fed 
 190 mg TSX-011, Fasted   
 380 mg TSX-011, Fed 
 570 mg TSX-011, Fed 
 
Period 2 Treatment: 380 mg TSX-011 BID dosing, Fed 
 
Period 3 Treatment: Treatments to be determined during dose-adjusted adaptive 
design period. TSX-011 dose adjustment permitted on Day 16 and Day 26 based on 6 
hours post-dose (± 15 minutes) testosterone level on Day 8 and Day 19, respectively; 
dosing period of 15 days. See Table 1 and Table 2 of this SAP. 
 
 
 SOFTWARE  
All statistical analyses performed by PAREXEL will be performed using Statistical 
Analysis Software (SAS®) (SAS® Institute Inc., Cary, North Carolina, United States 
of America [USA]) Version 9.2 or higher. The PK analysis will be performed using 
Phoenix® WinNonlin® Software Version 6.3 or higher (Certara, L.P., 9666 Olive 
Blvd, Suite 425, St. Louis MO 63132). 
6. 
Subject and Treatment Information 
6.1 
Subject Disposition 
The completion status, date of completion or discontinuation, the reason for 
discontinuation, and the date of withdrawal will be listed (Listing 16.2.1). The number 
of subjects enrolled and the frequency and percentage of subjects completing the 


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Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
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study, subjects withdrawing early, and primary reason for withdrawal will be 
summarized overall subjects enrolled (Table 14.1.1). The number and percent of 
subjects in the safety population and PK population will be summarized overall 
subjects enrolled.   
6.2 
Eligibility Criteria and Protocol Deviations 
Listing 16.2.2.1 will display all enrolled subjects who did not meet an inclusion 
criterion and all enrolled subjects who met an exclusion criterion. 
 
All reported protocol deviations will be listed (Listing 16.2.2.2).  
6.3 
Exclusion Tests  
Results of all exclusion tests (serology, drug, and alcohol screen) will be listed 
(Listing 16.2.2.3).  
6.4 
Demographic Data  
Demographic information will be listed (Listing 16.2.4.1).  Descriptive statistics will 
be obtained for the continuous variables: height, age, BMI, and body weight presented 
overall subjects enrolled (Tables 14.1.2).  Frequencies and percentage of subjects will 
be tabulated overall subjects enrolled for the categorical variables ethnicity, race, and 
gender (Tables 14.1.3).   
6.5 
Medical History 
Medical history data will be listed for each subject. Medical history will be coded 
using Medical Dictionary Regulatory Activities (MedDRA Version 20.1). Only those 
body systems where a condition or abnormality has been reported will be listed 
(Listing 16.2.4.2). 
6.6 
Concomitant Medication 
Prior and concomitant medications will be listed by subject (Listings 16.2.5.1 and 
16.2.5.2, respectively). Medications will be coded using WHODDE version 
September 2017. 
6.7 
Dose Administration 
Listing 16.2.5.3 will present subject number, treatment, period, visit, and the date and 
time of dose administration of TSX-011.  


PAREXEL International 
Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
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7. 
Pharmacokinetic Concentrations and Parameters 
Creation and delivery of all pharmacokinetic outputs for concentrations and 
parameters will be the responsibility of the sponsor. 
 
The PK sample concentrations for all subjects for each period will be summarized 
for each nominal sample time using minimum, maximum, median, standard 
deviation, and geometric mean. 
 
The following descriptive statistics will be presented in PK parameter summary 
tables: n (number of non-missing observations), arithmetic mean, SD, median, 
minimum, maximum, and geometric mean. 
 
Descriptive statistics and statistical analyses will be calculated using un-rounded 
results. All PK tables will be presented in units of ng/mL. 
7.1 
Plasma Concentrations 
The minimum and maximum statistics for Cmax and summaries of PK concentrations 
will reflect the rounding shown in the source data as provided by the bioanalytical 
laboratory. 
Pharmacokinetic concentration data for TSX-011 administration will be listed by 
subject, period, and treatment.  Actual sampling times relative to dosing, nominal 
scheduled times, and the difference between the actual and nominal sample time will 
also be listed. PK concentrations presented will include only actual total testosterone 
concentrations.  
8. 
Safety Analysis 
The analysis of the safety variables will be conducted using the safety population. 
8.1 
Adverse Events 
 
All verbatim AE terms reported will be coded according to MedDRA, version 20.1. 
Adverse events will be categorized as: 
 Treatment emergent AEs (TEAEs) are defined as any AEs that occur after first 
dose of IP 
 Non-treatment emergent AEs (NTEAE): AEs whose onset occurred before the 
administration of first IP  
 
All AE data as captured in ClinBase will be listed for each subject (Listing 16.2.7.1). 
All serious AEs (SAEs) will be listed (Listing 16.2.7.2). A listing of all AEs leading 
to treatment discontinuation will be presented, if applicable (Listing 16.2.7.3).   


PAREXEL International 
Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
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Unless specified otherwise, all adverse event summaries will include the TEAEs only 
and adverse event summary counts of AEs will be the number of subjects reporting 
adverse events and not the number of events reported. The number and percentage of 
subjects with adverse events will be tabulated by body system and preferred term by 
treatment. A subject with multiple adverse events within a body system is only 
counted once towards the total of that body system.  If the same AE (preferred term) 
is reported several times for the same subject within a given treatment, it will only 
appear once for that specified treatment in the summary tables. 
For purposes of the summary tables, AEs will be classified as either being related to 
study drug or not related. AEs related to study drug will include AEs classified as 
‘Definite’, 'Probable', or ‘Possible’. AEs not related to study drug will include AEs 
that are ‘Not related’.  
As defined in the protocol, within the source data all AEs will be assigned a severity 
grade of: Mild, Moderate, or Severe. For subjects with multiple adverse events of the 
same preferred term and of different severities, the AE with the highest assessment of 
severity will be used in the summaries presented by severity.   
A general summary of all treatment-emergent adverse events (Table 14.3.1.1) will 
show the number and percentage of subjects, as well as the number of events, 
according to the following categories: 
 All treatment emergent adverse events  
 Treatment emergent adverse events ‘Related’ to TSX-011 
 Mild treatment emergent adverse events 
 Moderate treatment emergent adverse events 
 Severe treatment emergent adverse events 
 Serious treatment emergent adverse events 
 Treatment emergent adverse events leading to early termination 
 Deaths 
 
Other summary tables for adverse events will include: 
 Table 14.3.1.2: Number and Percentage of Subjects with Treatment Emergent 
Adverse Events by System Organ Class, Preferred Term, and Treatment 
 Table 14.3.1.3: Number and Percentage of Subjects with Treatment Emergent 
Adverse Events ‘Related to the IP’ by System Organ Class, Preferred Term, 
Severity, and Treatment. 
 Table 14.3.1.4: Number and Percentage of Subjects with Treatment Emergent 
Adverse Events ‘Not Related to the IP’ by System Organ Class, Preferred Term, 
Severity, and Treatment. 
For tabulations of AEs by treatment, any AE that starts on or after administration of 
the first dose period 1 (i.e. Period 1, 190 mg fed) and before the second dose period 1 


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Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
Final 1.0 
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(Period 1, 190 mg fasted), will be assigned to the first treatment dose period 1.  Any 
AE occurring after the second dose period 1 (Period 1, 190 mg fasted) and before the 
third dose period 1 (Period 1, 380 mg), will be assigned to the second dose; and any 
AE occurring after the third dose period 1 (Period 1, 380 mg) and before the first dose 
of treatment period 2 (Period 2, 380 mg) will be assigned to the period 1 third dose. 
If a subject has multiple AEs with the same preferred term but occurring after each 
dose administration, then one AE will be counted for each treatment.  Adverse events 
that emerge in one treatment period and carry over into the next period will be 
attributed to only the period in which the AE emerged. 
8.2 
Clinical Safety Laboratory Tests (Hematology, Chemistry, Urinalysis) 
8.2.1 Hematology and Chemistry 
 
A by-subject listing of all observed chemistry and hematology laboratory data will be 
provided (Listings 16.2.8.1 and 16.2.8.2, respectively).  Laboratory results outside the 
normal range will be flagged.  The abnormal values will be flagged with ‘L’ (low) for 
values below the lower limit of the laboratory’s normal range or ‘H’ (high) for values 
above the upper limit of the laboratory’s normal range. Abnormal values will be 
graded as not clinically significant (NCS) or clinically significant (CS). Clinically 
significant laboratory results will be included in the AE listings.   
 
The observed values of all safety laboratory assessments for clinical chemistry and 
hematology will be summarized using descriptive statistics showing the number of 
observations (n), mean, median, SD, minimum, and maximum value. Table 
summaries will be presented overall treatments for each time point: (Chemistry Table 
14.3.2.1, Hematology Table 14.3.2.2). 
 
Baseline values for all clinical chemistry and hematology parameters will be 
categorized as being below the normal range (Low), within the normal range 
(Normal), and above the normal range (High).  Shift from baseline tables will present 
the frequency and percentage of subjects who have observations that are Normal, 
Low, or High. Shift tables will be presented by time point overall treatments (Tables 
14.3.2.3 and 14.3.2.4). For shift tables, baseline will be the last laboratory assessment 
prior to the first dose in Period 1. 
 
Only laboratory parameters noted in Section 4.2.2 of this SAP will be tabulated.   
8.2.2 Urinalysis 
 
Urinalysis test results for pH, specific gravity, protein, glucose, ketones, bilirubin, 
blood, nitrite, urobilinogen, leukocyte esterase will be listed (Listing 16.2.8.3). All 
positive findings in the microscopic examination will be listed (Listing 16.2.8.4).  


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Protocol Number TT-018 
Final 1.0 
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Observations outside the normal range will be flagged.  The abnormal quantitative 
values will be flagged with ‘L’ for values below the lower limit of the laboratory’s 
normal range, ‘H’ for values above the upper limit of the laboratory’s normal range, or 
‘Ab’ for abnormal qualitative test results.  All original and unscheduled assessments 
will be listed.  Clinically significant laboratory results that are considered by the 
investigator to be AEs will be included in the AE listings. 
8.2.3 Laboratory Comments 
 
A listing of laboratory comments will be provided (Listing 16.2.8.5). 
8.2.4 Other Laboratory Assessments 
 
Results for testosterone and PSA will be listed for each subject. 
 
8.3 
Vital Signs 
 
The observed data for blood pressure (systolic and diastolic), heart rate (pulse), body 
temperature and respiration rate will be listed by subject, treatment, and time point 
(Listings 16.2.9.1).  Change from baseline for blood pressure (systolic and diastolic), 
heart rate (pulse), body temperature and respiration rate will be derived and listed by 
subject, treatment, and time point (Listing 16.2.9.2).  
 
In the calculation of change from baseline, the baseline value for each period will be 
the last assessment collected prior to first dosing in each treatment period.  
 
For systolic and diastolic blood pressure, heart rate, body temperature and respiration 
rate the observed and change from baseline data will be summarized by treatment and 
time point. Summaries will include tables of descriptive statistics showing the number 
of observations (n), mean, SD, median, minimum, and maximum value (Tables 
14.3.3.1 and 14.3.3.2). 
 
8.4 
12-Lead Safety ECG 
 
Raw quantitative results for: PR interval, QRS interval, RR interval, QT interval,  
QTcB (corrected QT according to Bazett), QTcF (corrected QT according to 
Fridericia), and heart rate will be listed for each subject (Listing 16.2.10.1).  Change 
from baseline will be derived and listed for each subject for parameters QT, QTcB 
and QTcF (Listing 16.2.10.2).  
 


PAREXEL International 
Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
Page 33 of 84 
 
 
In the calculation of change from baseline, the baseline value for each period will be 
the last assessment collected prior to first dosing in each treatment period. 
 
The overall qualitative ECG assessment for each subject will be listed by treatment, 
subject, and time point (Listing 16.2.10.3). 
 
For QT, QTcB, and Q TcF the observed and change from baseline data will be 
summarized by time point. Summaries will include tables of descriptive statistics 
showing the number of observations (n), mean, SD, median, minimum, and maximum 
value (Table 14.3.4.1).  
 
The number and percentage of subjects having observed QT, QTcB, and QTcF values 
that satisfy the following conditions will be summarized by time point (Table 
14.3.4.2): 
 
 ≤ 450 msec 
 450 < to ≤ 480 msec 
 480 < to ≤ 500 msec 
 > 500 msec 
 
The number and percentage of subjects having change from baseline QT, QTcB, and 
QTcF values that satisfy the following conditions will be presented by time point 
(Table 14.3.4.3): 
 
 ≤ 0 msec 
 > 0 to ≤ 30 msec 
 > 30 to ≤ 60 msec 
 > 60 msec 
 
8.5 
Physical Examination 
 
All abnormal physical examination findings (pre and post-dose assessments) will be 
listed (Listing 16.2.11).  
8.6 
IPSS Questionnaire 
 
Results from the IPS questionnaire will be listed for each subject by treatment period 
(Listing 16.2.12.1).  
8.7 
QOL Questionnaire 
 


PAREXEL International 
Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
Page 34 of 84 
 
 
Results from the QOL questionnaire will be listed for each subject by treatment 
period (Listing 16.2.12.2). Including will be results for IPSS, AMS scale, MSAM-7, 
and PDQ. 
 
9. 
Reporting Output 
 
The tables, listings, figures and any non-descriptive statistical analysis will be 
produced using Unix SAS Software (Version 9.0 or higher).  The REPORT 
procedure will be used to produce all tables and listings; SAS/GRAPH will be used to 
produce all figures.   
 
Tables, listings, and figures will be produced in the order that they appear in the 
textual sections of the plan.  
 
All tables, listings, and graphs will be produced to landscape orientation using Courier 
New 8pt font and will be incorporated into a MS Word document as a (RTF) rich text 
file (margins: top, left, right, and bottom: 1 inch).  A separate RTF document will be 
created for each table, figure and listing individually. 
 
 
10. 
References 
 
1. Phoenix® WinNonlin® version 6.3 or higher (Certara, L.P., 9666 Olive Blvd, Suite 
425, St. Louis MO 63132). 
 


PAREXEL International 
Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
Page 35 of 84 
 
 
11. 
Summary Tables 
 
 
 
Table 14.1.1 
Subject Disposition  
Table 14.1.2 
Demographics - Continuous Variables  
Table 14.1.3 
Demographics - Categorical Variables  
Table 14.3.1.1 
Summary of Treatment Emergent Adverse Events   
Table 14.3.1.2 
Number and Percentage of  Subjects with Treatment Emergent 
Adverse Events by System Organ Class, Preferred Term, and 
Treatment  
Table 14.3.1.3 
Number and Percentage of Subjects with Treatment Emergent  
Adverse Events ‘Related to the IMP’ by System Organ Class,  
Preferred Term, Severity, and Treatment 
Table 14.3.1.4 
Number and Percentage of Subjects with Treatment Emergent  
Adverse Events ‘Not Related to the IMP’ by System Organ   
Class, Preferred Term, Severity, and Treatment 
Table 14.3.2.1 
Clinical Laboratory Chemistry Summary of Observed Values  
Table 14.3.2.2 
Clinical Laboratory Hematology Summary of Observed Values 
Table 14.3.2.3 
Clinical Laboratory Chemistry Shift From Baseline to Day 5 
Table 14.3.2.4 
Clinical Laboratory Hematology Shift From Baseline to Day 5 
Table 14.3.3.1 
Vital Signs Blood Pressure and Heart Rate Summary of 
Observed and Values 
Table 14.3.3.2 
Vital Signs Blood Pressure and Heart Rate Summary of Change 
From Baseline Values 
Table 14.3.4.1 
12-Lead ECG – Summary of Observed and Change From 
Baseline Values  
Table 14.3.4.2 
12-Lead ECG – Categorical Summary of Observed Values  
Table 14.3.4.3 
12-Lead ECG – Categorical Summary of Change From Baseline  
 


PAREXEL International 
Statistical Analysis Plan 
 
TesoRx Pharma, LLC 
Protocol Number TT-018 
Final 1.0 
13 June 2018 
 
 
 
Page 36 of 84 
 
 
 
12. 
Listings 
Listing 16.2.1 
Subject Disposition 
 Listing 16.2.2.1 
 Enrolled Subjects Who Did Not Meet All Eligibility Criteria 
 Listing 16.2.2.2 
 Protocol Deviations  
Listing 16.2.2.3 
Exclusion Tests  
Listing 16.2.4.1 
Demographics 
Listing 16.2.4.2 
Medical History  
Listing 16.2.5.1 
Prior Medications  
Listing 16.2.5.2 
Concomitant Medications 
Listing 16.2.5.3 
Dose Administration  
Listing 16.2.7.1 
Adverse Events 
Listing 16.2.7.2 
Serious Adverse Events 
Listing 16.2.7.3 
Adverse Events Leading to Discontinuation 
Listing 16.2.8.1 
Clinical Laboratory Chemistry – Observed Values 
Listing 16.2.8.2 
Clinical Laboratory Hematology – Observed Values 
Listing 16.2.8.3 
Clinical Laboratory Urinalysis – Observed Values 
Listing 16.2.8.4 
Clinical Laboratory Urinalysis – Positive Microscopic Findings 
Listing 16.2.8.5 
Clinical Laboratory Comments 
Listing 16.2.8.6 
Other Clinical Laboratory Results 
Listing 16.2.9.1 
Vital Signs Observed Values  
Listing 16.2.9.2 
Vital Signs Change from Baseline  
Listing 16.2.10.1 
12 Lead Safety ECG Quantitative Findings 
Listing 16.2.10.2 
12 Lead Safety ECG Change From Baseline 
Listing 16.2.10.3 
12 Lead Safety ECG – Qualitative Assessment 
Listing 16.2.11 
Physical Examination Abnormal Findings 
Listing 16.2.12.1 
QOL questionnaire - International Prostrate Symptom Score (IPSS) 
Listing 16.2.12.2 
QOL questionnaire – AMS  
Listing 16.2.12.3 
QOL questionnaire – Male Sexual Dysfunction Multinational Survey of 
the Aging male (MSAM-7) 
Listing 16.2.12.4 
QOL questionnaire – Psychosexual Daily Questionnaire (PDQ) 


PAREXEL International 
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Final 1.0  
 
13 June 2018 
 
 
 
   
                                                                                                                                                                                                             Page 37 of 84 
 
13. 
Table Shells 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 38 of 84 
 
TesoRx Pharma, LLC 
Page X of Y 
Protocol Number: TT-018 
Table 14.1.1 
Subject Disposition 
 
 
 
 
Overall 
N = x 
Enrolled 
nn (nn.n%) 
Completed the Study 
nn (nn.n%) 
Discontinued from the Study 
nn (nn.n%) 
Safety Population 
nn (nn.n%) 
Pharmacokinetic Population 
nn (nn.n%) 
 
 
Reason for Discontinuation 
 
Adverse Event  
nn (nn.n%) 
Protocol Deviation 
nn (nn.n%) 
Consent Withdrawn  
nn (nn.n%) 
Lost to Follow-Up 
nn (nn.n%) 
Death 
nn (nn.n%) 
Other 
nn (nn.n%) 
 
 
 
 


PAREXEL International 
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Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 39 of 84 
 
TesoRx Pharma, LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
Table 14.1.2 
Demographics – Continuous Variables  
 
 
 
Statistic 
Overall 
N = x 
Age 
(years) 
n 
nn 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min 
xx 
Max 
xx 
 
 
 
Height 
(cm) 
n 
nn 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min 
xx 
Max 
xx 
 
 
 
Weight 
(kg) 
n 
nn 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min 
xx 
Max 
xx 
 
 
 
BMI 
(kg/m^2) 
n 
nn 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min 
xx 
Max 
xx 
 
 


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Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 40 of 84 
 
TesoRx Pharma, LLC 
Page X of Y 
Protocol Number: TT-018 
Table 14.1.3 
Demographics – Categorical Variables 
 
 
 
Overall 
N = x 
Ethnicity 
 
Hispanic/Latino 
nn (nn.n%) 
   Non Hispanic/Latino 
nn (nn.n%) 
 
 
Race 
 
White  
nn (nn.n%) 
American Indian/Alaska Native 
nn (nn.n%) 
Asian 
nn (nn.n%) 
Native Hawaiian or other Pacific Islander 
nn (nn.n%) 
Black/African American 
nn (nn.n%) 
Other 
nn (nn.n%) 
 
 
Gender 
 
Male 
nn (nn.n%) 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 41 of 84 
 
 
 
TesoRx Pharma, LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Protocol Number: TT-018 
 
 
 
Table 14.3.1.1 
Summary of Treatment Emergent Adverse Events   
 
  
 
 
Treatment 
190 mg  
TSX-011 
Fasted 
N = x 
 
nn (%) E 
190 mg  
TSX-011 
Fed 
N = x 
 
nn (%) E 
380 mg  
TSX-011 
Fed 
N = x 
 
nn (%) E 
570 mg  
TSX-011 
Fed 
N = x 
 
nn (%) E 
380 mg 
TSX-011 
BID Fed 
N = x 
 
nn (%) E 
 
Period 3 
Adaptive-Dose 
Design 
Treatment 
 
nn (%) E 
All AEs 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
AEs ‘Related to TSX-011’ 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
AEs ‘Related to both’ 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
Mild AEs 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
Moderate AEs 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
Severe AEs 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
Deaths 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
Serious AEs 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
AEs Leading to discontinuation of IMP 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
 
 
 
 
TEAE = Treatment Emergent Adverse Event  
nn = Number of Subjects with TEAEs 
N  = Number of Subjects Exposed  
(nn.n%) = nn/N x 100 
E = Number of AEs 
 
 
 
 


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SAP Shells 
 
Final 1.0  
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                                                                                                                                                                                                                Page 42 of 84 
 
 
 
 
 
TesoRx Pharma, LLC 
Page X of Y 
Protocol Number: TT-018 
 
Table 14.3.1.2 
Number and Percentage of Subjects with Treatment Emergent Adverse Events 
by System Organ Class, Preferred Term, and Treatment  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
System Organ Class 
   Preferred Term 
Treatment 
190 mg  
TSX-011 
Fasted 
N = x 
190 mg  
TSX-011 
Fed 
N = x 
380 mg  
TSX-011 
Fed 
N = x 
570 mg  
TSX-011 
Fed 
N = x 
380 mg  
TSX-011  
BID Fed 
N = x 
 
Period 3 
Adaptive-
Dose  
Design 
Treatment 
 
 
 
 
 
 
 
System Organ Class 1 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 1 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 2 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 3 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term xx 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
 
 
 
 
 
 
 
System Organ Class 2 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 1 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 2 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 3 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term xx 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
 
 
 
 
 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 43 of 84 
 
 
TesoRx Pharma, LLC 
Page X of Y 
Protocol Number: TT-018 
 
 
Table 14.3.1.3 
Number and Percentage of Subjects with Treatment Emergent Adverse Events ‘Related to IP’ 
by System Organ Class, Preferred Term, Severity, and Treatment  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
System Organ Class 
   Preferred Term 
 
 
 
 
 
Severity 
 
Treatment 
190 mg  
TSX-011 
Fasted 
N = x 
190 mg  
TSX-011 
Fed 
N = x 
380 mg  
TSX-011 
Fed 
N = x 
570 mg  
TSX-011 
Fed 
N = x 
380 mg  
TSX-011  
BID Fed 
N = x 
 
Period 3 
Adaptive-
Dose  
Design 
Treatment 
System Organ Class 1 
Mild 
Moderate 
Severe 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 1 
Mild 
Moderate 
Severe 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term xx 
Mild 
Moderate 
Severe 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
 
 
 
 
 
 
 
 
System Organ Class 2 
Mild 
Moderate 
Severe 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 1 
Mild 
Moderate 
Severe 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term xx 
Mild 
Moderate 
Severe 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
Etc… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 44 of 84 
 
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Page X of Y 
Protocol Number: TT-018 
 
 
Table 14.3.1.4 
Number and Percentage of Subjects with Treatment Emergent Adverse Events ‘Not Related to IP’ 
by System Organ Class, Preferred Term, Severity, and Treatment  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
System Organ Class 
   Preferred Term 
 
 
 
 
 
Severity 
 
Treatment 
190 mg  
TSX-011 
Fasted 
N = x 
190 mg  
TSX-011 
Fed 
N = x 
380 mg  
TSX-011 
Fed 
N = x 
570 mg  
TSX-011 
Fed 
N = x 
380 mg  
TSX-011  
BID Fed 
N = x 
 
Period 3 
Adaptive-
Dose  
Design 
Treatment 
System Organ Class 1 
Mild 
Moderate 
Severe 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 1 
Mild 
Moderate 
Severe 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term xx 
Mild 
Moderate 
Severe 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
 
 
 
 
 
 
 
 
System Organ Class 2 
Mild 
Moderate 
Severe 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 1 
Mild 
Moderate 
Severe 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term xx 
Mild 
Moderate 
Severe 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
Etc… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 45 of 84 
 
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Page X of Y 
Protocol Number: TT-018 
Table 14.3.2.1 
Clinical Laboratory Chemistry - Summary of Observed Values  
 
Lab Parameter = Lab Parameter (unit) 
 
 
 
Visit 
Statistic 
Overall 
N = x 
Screening 
 
n 
nn 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min 
xx 
Max 
xx 
 
 
 
 
Day -1 
 
n 
nn 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min 
xx 
Max 
xx 
 
 
 
 
Day 2 
 
n 
nn 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min 
xx 
Max 
xx 
 
 
 
 
n 
nn 
 
Mean 
xx.x 
Day 2 
SD 
xx.xx 
 
Median 
xx.x 
Period 2 
Min 
xx 
 
Max 
xx 
 
 
 
 
n 
nn 
 
Mean 
xx.x 
Day 8 
SD 
xx.xx 
 
Median 
xx.x 
Period 2 
Min 
xx 
 
Max 
xx 
Etc… 
 
 
 
 
 


PAREXEL International 
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                                                                                                                                                                                                                Page 46 of 84 
 
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Protocol Number: TT-018 
 
Table 14.3.2.2 
Clinical Laboratory Hematology - Summary of Observed Values  
 
Lab Parameter = Lab Parameter (unit) 
 
 
 
Visit 
Statistic 
Overall 
N = x 
Screening 
 
n 
nn 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min 
xx 
Max 
xx 
 
 
 
 
Day -1 
 
n 
nn 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min 
xx 
Max 
xx 
 
 
 
 
Day 2 
 
n 
nn 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min 
xx 
Max 
xx 
 
 
 
 
n 
nn 
 
Mean 
xx.x 
Day 2 
SD 
xx.xx 
 
Median 
xx.x 
Period 2 
Min 
xx 
 
Max 
xx 
 
 
 
 
n 
nn 
 
Mean 
xx.x 
Day 8 
SD 
xx.xx 
 
Median 
xx.x 
Period 2 
Min 
xx 
 
Max 
xx 


PAREXEL International 
SAP Shells 
 
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13 June 2018 
 
                                                                                                                                                                                                                Page 47 of 84 
 
  
 
TesoRx Pharma, LLC 
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Protocol Number: TT-018 
 
Table 14.3.2.3.1 
Clinical Laboratory Chemistry – Shift From Baseline to Maximum Value Post-Dose 
 
Lab Parameter = Lab Parameter (unit) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment 
Period 
 
Shift  
From  
Baseline  
Baseline (Day -1) 
Low 
Normal 
High 
Period 1 
Low 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
Normal 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
High 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
 
 
 
 
 
    
   Period 2 
 
Low 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
Normal 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
High 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
 
 
 
 
 
 
Low 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
   Period 3 
Normal 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
 
High 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
 
 
 
 
 
 
 
 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 48 of 84 
 
TesoRx Pharma, LLC 
Page X of Y 
Protocol Number: TT-018 
 
Table 14.3.2.3.2 
Clinical Laboratory Chemistry – Shift From Baseline to Minimum Value Post-Dose 
 
Lab Parameter = Lab Parameter (unit) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment 
Period 
 
Shift  
From  
Baseline  
Baseline (Day -1) 
Low 
Normal 
High 
Period 1 
Low 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
Normal 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
High 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
 
 
 
 
 
    
   Period 2 
 
Low 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
Normal 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
High 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
 
 
 
 
 
 
Low 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
   Period 3 
Normal 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
 
High 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
 
 
 
 
 
 
 
 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 49 of 84 
 
TesoRx Pharma, LLC 
Page X of Y 
Protocol Number: TT-018 
 
Table 14.3.2.4.1 
Clinical Laboratory Hematology – Shift From Baseline to Maximum Value Post-Dose 
 
Lab Parameter = Lab Parameter (unit) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment 
Period 
 
Shift  
From  
Baseline  
Baseline (Day -1) 
Low 
Normal 
High 
Period 1 
Low 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
Normal 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
High 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
 
 
 
 
 
    
   Period 2 
 
Low 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
Normal 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
High 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
 
 
 
 
 
 
Low 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
   Period 3 
Normal 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
 
High 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
 
 
 
 
 
 
 
 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 50 of 84 
 
TesoRx Pharma, LLC 
Page X of Y 
Protocol Number: TT-018 
 
Table 14.3.2.4.2 
Clinical Laboratory Hematology – Shift From Baseline to Minimum Value Post-Dose 
 
Lab Parameter = Lab Parameter (unit) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment 
Period 
 
Shift  
From  
Baseline  
Baseline (Day -1) 
Low 
Normal 
High 
Period 1 
Low 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
Normal 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
High 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
 
 
 
 
 
    
   Period 2 
 
Low 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
Normal 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
High 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
 
 
 
 
 
 
Low 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
   Period 3 
Normal 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
 
High 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
 
 
 
 
 
 
 
 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 51 of 84 
 
TesoRx Pharma, LLC 
Page X of Y 
Protocol Number: TT-018 
Table 14.3.3.1 
Vital Signs Summary of Observed Values  
 
Parameter = Systolic Blood Pressure (mmHg) 
Visit 
Statistic 
 
Overall 
N = x 
Screening 
 
n 
nn 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min 
xx 
Max 
xx 
 
 
 
Day -1 
 
n 
nn 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min 
xx 
Max 
xx 
 
 
 
Day 1, 
Time 0 
 
n 
nn 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min 
xx 
Max 
xx 
 
 
 
Day 1, 6 
hours 
post 
n 
nn 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min 
xx 
Max 
xx 
Etc… 
 
 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 52 of 84 
 
TesoRx Pharma, LLC 
Page X of Y 
Protocol Number: TT-018 
Table 14.3.3.2 
Vital Signs Summary of Change from Baseline  
 
Parameter = Systolic Blood Pressure (mmHg) 
 
Visit 
Statistic 
 
Overall 
N = x 
 
Day 1, 6 
hours 
post  
 
n 
nn 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min 
xx 
Max 
xx 
 
 
 
 
Day 1, 24 
hours 
post  
 
n 
nn 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min 
xx 
Max 
xx 
 
 
 
Period 2, 
Day 1, 8 
hours 
post  
 
n 
nn 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min 
xx 
Max 
xx 
 
 
 
Period 2, 
Day 1, 16 
hours 
post  
 
n 
nn 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min 
xx 
Max 
xx 
Etc… 
 
 
 
 
Baseline in a given period is the last assessment prior to the first dose in that period.


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 53 of 84 
 
TesoRx Pharma, LLC 
Page X of Y 
Protocol Number: TT-018 
 
Table 14.3.4.1 
12 Lead ECG – Summary of Observed and Change From Baseline Values  
 
Parameter = QT (msec) 
 
Visit 
Statistic 
Observed 
 
N = x 
Change From 
Baseline 
N = x 
Screening 
 
n 
nn 
 
Mean 
xx.x 
 
SD 
xx.xx 
 
Median 
xx.x 
 
Min 
xx 
 
Max 
xx 
 
 
 
 
 
Day -1 
 
n 
nn 
 
Mean 
xx.x 
 
SD 
xx.xx 
 
Median 
xx.x 
 
Min 
xx 
 
Max 
xx 
 
 
 
 
 
Day 2 
 
n 
nn 
nn 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min 
xx 
xx 
Max 
xx 
xx 
 
 
 
 
 
n 
nn 
nn 
 
Mean 
xx.x 
xx.x 
Period 2 
SD 
xx.xx 
xx.xx 
Day 2 
Median 
xx.x 
xx.x 
 
Min 
xx 
xx 
 
Max 
xx 
xx 
Etc… 
 
 
 
 
 
 
 
Baseline = Day -1 
QTcB = QT corrected according to Bazett, QTcF = QT corrected according to Fridericia. 
 
Programming Notes: Table will be expanded to include QT, QTcB, and QTcF 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 54 of 84 
 
TesoRx Pharma, LLC 
Page X of Y 
Protocol Number: TT-018 
 
Table 14.3.4.2 
12 Lead ECG – Categorical Summary of Observed Values   
 
Parameter = QT (msec) 
 
 
Visit 
 
Category (unit) 
Overall 
  
N = x 
Screening 
≤ 450  
nn (nn.n%) 
450 < to ≤ 480 
nn (nn.n%) 
480 < to ≤ 500 
nn (nn.n%) 
>500 
nn (nn.n%) 
 
 
 
Day -1 
 
≤ 450  
nn (nn.n%) 
450 < to ≤ 480 
nn (nn.n%) 
480 < to ≤ 500 
nn (nn.n%) 
>500 
nn (nn.n%) 
 
 
 
 
Day 2 
 
≤ 450  
nn (nn.n%) 
450 < to ≤ 480 
nn (nn.n%) 
480 < to ≤ 500 
nn (nn.n%) 
>500 
nn (nn.n%) 
Etc… 
 
 
 
 
 
 
 
QTcB = QT corrected according to Bazett, QTcF = QT corrected according to Fridericia. 
 
 
Programming Notes:  
Table will be expanded to include QT, QTcB, and QTcF 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 55 of 84 
 
 
TesoRx Pharma, LLC 
Page X of Y 
Protocol Number: TT-018 
 
Table 14.3.4.3 
12 Lead ECG – Categorical Summary of Change from Baseline   
All Subjects as Treated 
 
 Parameter = QT (msec) 
 
 
Visit 
 
Category (unit) 
Overall 
  
N = x 
 
Day 2 
 
<= 0 
nn (nn.n%) 
>0 to ≤ 30  
nn (nn.n%) 
>30 to ≤ 60 
nn (nn.n%) 
>60 
nn (nn.n%) 
 
 
 
 
<= 0 
nn (nn.n%) 
 
>0 to ≤ 30  
nn (nn.n%) 
Period 2 Day 2 
>30 to ≤ 60 
nn (nn.n%) 
 
>60 
nn (nn.n%) 
 
 
 
 
<= 0 
nn (nn.n%) 
 
>0 to ≤ 30  
nn (nn.n%) 
 
>30 to ≤ 60 
nn (nn.n%) 
 
>60 
nn (nn.n%) 
Period 2 Day 8 
 
 
 
<= 0 
nn (nn.n%) 
 
>0 to ≤ 30  
nn (nn.n%) 
 
>30 to ≤ 60 
nn (nn.n%) 
 
>60 
nn (nn.n%) 
 
 
Baseline = Day -1 
QTcB = QT corrected according to Bazett, QTcF = QT corrected according to Fridericia. 
 
Programming Notes:  
Table will be expanded to include QT, QTcB, and QTcF 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 56 of 84 
 
14. 
Listing Shells 
 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 57 of 84 
 
 
TesoRx Pharma, LLC 
Page X of Y 
Protocol Number: TT-018 
 
 
 
Listing 16.2.1 
Subject Disposition   
 
 
 
 
 
Subject 
 
Completion Status 
 
 
 
If Discontinued, 
Date of Withdrawal 
Reason For 
Discontinuation 
 
 
 
Period 
of Withdrawal 
 
 
 
Study Day 
of Withdrawal 
 
Completed  
 
 
 
 
 
Discontinued  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 58 of 84 
 
TesoRx Pharma, LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
 
 
Listing 16.2.2.1 
Enrolled Subjects Who Did Not Meet All Eligibility Criteria 
 
 
 
 
 
 
Subject 
 
 
 
Criteria Category 
 
 
 
Criteria Description 
 
 
 
Response 
 
Inclusion 
 
No  
 
Exclusion 
 
Yes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 59 of 84 
 
TesoRx Pharma, LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
 
Listing 16.2.2.2 
Protocol Deviations 
 
 
Subject 
 
Period 
Visit 
Classification Explanation 
Date of 
Deviation 
Time of 
Deviation 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 60 of 84 
 
TesoRx Pharma, LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
 
 
Listing 16.2.2.3 
Exclusion Tests   
Serology, Drug, Alcohol Screen  
 
 
 
 
 
 
Subject 
 
 
 
 
 
Period 
Visit 
 
Collection 
Date 
 Collection 
Time 
 
Exclusion Test 
 
Result 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
        
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 61 of 84 
 
  
TesoRx Pharma, LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
Listing 16.2.4.1  
Demographics  
 
 
 
 
 
 
Subject 
Gender 
 
 
 
 
 
Ethnicity 
 
 
 
 
 
Race 
 
 
 
 
Age 
(yrs) 
Height  
(cm) 
Weight 
(kg) 
 
 
 
 
BMI 
(kg/m^2) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 62 of 84 
 
  
TesoRx Pharma, LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
 
 
Listing 16.2.4.2 
 Medical History   
 
 
 
 
 
Subject 
Body System 
>MedDRA Preferred Term 
>>System Organ Class 
Condition or 
Abnormality 
Remark 
Date of 
Onset 
Date of 
Resolution 
Status 
 
 
 
 
 
 
Chronic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 63 of 84 
 
 
TesoRx Pharma, LLC 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
Listing 16.2.5.1 
Prior Medications 
Medications Taken 30 Days Prior to Screening until First Dose of Study Medication 
 
 
 
 
 
 
Subject 
 
Medication 
 
Start Date 
Stop 
Date 
Dose (units) 
 
 
 
 
Ongoing? 
 
 
 
 
Reason for use 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 64 of 84 
 
TesoRx Pharma, LLC 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
Listing 16.2.5.2 
Concomitant Medications   
 
 
 
 
 
Subject 
Medication  
Total dose /  
administration  
Route 
 
 
 
Frequency 
Start 
Date  
Time 
Stop 
Date  
Time 
Reason 
for use 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 65 of 84 
 
TesoRx Pharma, LLC 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
 
Listing 16.2.5.3 
Study Drug Administration 
 
 
 
 
 
 
 
 
 
Subject 
 
 
 
Period 
 
 
 
 
 
 
Treatment 
Visit 
Date of 
Dose 
Time of 
Dose 
Drug 
Name 
Dose 
Administered 
 
 
 
 
 
Dose  
Unit 
 
 
 
 
 
Dose 
Frequency 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 66 of 84 
 
 
TesoRx Pharma, LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
 
Listing 16.2.7.1 
Adverse Events 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subject 
 
 
 
 
 
 
 
 
 
 
 
Period 
Treatment 
Adverse Event 
>MedDRA Preferred Term 
>>System Organ Class  
Start 
 Date  
 Time 
   Stop  
Date  
 Time 
Severity  
Action 
Taken 
 
 
 
 
 
 
 
 
Rela-
tion-
ship 
to IP 
 
 
 
 
 
 
 
 
 
Seri-
ous 
Out-
come 
 
 
 
 
 
 
 
Time 
relative 
to most 
recent 
dose  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 67 of 84 
 
 
TesoRx Pharma, LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
 
Listing 16.2.7.2 
Serious Adverse Events 
 
 
 
 
 
 
 
 
 
 
 
 
Subject 
 
 
 
 
 
 
 
 
 
 
 
Period 
Treatment 
Adverse Event 
>MedDRA Preferred Term 
>>System Organ Class  
Start 
 Date  
 Time 
   Stop  
Date  
 Time 
Severity  
Action 
Taken 
 
 
 
 
 
 
 
 
Rela-
tion-
ship 
to IP 
Out-
come 
 
 
 
 
 
 
 
Time 
relative 
to most 
recent 
dose  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 68 of 84 
 
TesoRx Pharma, LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
Listing 16.2.7.3 
Adverse Events Leading To Discontinuation  
 
 
 
 
 
 
 
 
 
 
 
 
 
Subject 
 
 
 
 
 
 
 
 
 
 
 
Period 
Treatment 
Adverse Event 
>MedDRA Preferred Term 
>>System Organ Class  
Start 
 Date  
 Time 
   Stop  
Date  
 Time 
Severity  
Action 
Taken 
 
 
 
 
 
 
 
 
Rela-
tion-
ship 
to IP 
 
 
 
 
 
 
 
 
 
 
Seri-
ous 
Out-
come 
 
 
 
 
 
 
 
Time 
relative 
to most 
recent 
dose  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 69 of 84 
 
TesoRx Pharma, LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
 
Listing 16.2.8.1 
Clinical Laboratory Chemistry - Observed Values  
 
 
 
 
 
 
 
 
Subject 
 
 
 
Period 
 
 
 
 
 
Treatment Visit 
Collection 
Date  
 
 
 
 
Collection 
Time 
 
 
Lab 
Parameter 1 
(unit) 
Lab  
parameter 2 
(unit) 
Lab 
parameter 3 
(unit) 
Lab 
parameter 4 
(unit) 
 
 
 
 
 
 
Result/Flag 
Result/Flag 
Result/Flag 
Result/Flag 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
H=High, L=Low, CS=Clinically Significant, NCS=Not Clinically Significant 
 
 
Programming Note: If Flag is present (H or L), clinical significance will be identified by ‘NCS’ or ‘CS’. 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 70 of 84 
 
TesoRx Pharma, LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
 
Listing 16.2.8.2 
Clinical Laboratory Hematology - Observed Values  
 
 
 
 
 
 
 
Subject 
 
 
 
Period 
 
 
 
 
 
Treatment Visit 
Collection 
Date  
 
 
 
 
Collection 
Time 
 
 
Lab 
Parameter 1 
(unit) 
Lab  
parameter 2 
(unit) 
Lab 
parameter 3 
(unit) 
Lab 
parameter 4 
(unit) 
 
 
 
 
 
 
Result/Flag 
Result/Flag 
Result/Flag 
Result/Flag 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
H=High, L=Low, CS=Clinically Significant, NCS=Not Clinically Significant 
 
 
Programming Note: If Flag is present (H or L), clinical significance will be identified by ‘NCS’ or ‘CS’. 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 71 of 84 
 
 
  
TesoRx Pharma, LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
Listing 16.2.8.3 
Clinical Laboratory Urinalysis - Observed Values  
 
 
 
 
 
 
Subject 
 
 
 
Period 
 
 
 
 
 
Treatment Visit 
Collection 
Date  
 
 
 
 
Collection 
Time 
 
 
Lab 
Parameter 1 
(unit) 
Lab  
parameter 2 
(unit) 
Lab 
parameter 3 
(unit) 
Lab 
parameter 4 
(unit) 
 
 
 
 
 
 
Result/Flag 
Result/Flag 
Result/Flag 
Result/Flag 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
H=High, L=Low, AB=Abnormal, CS=Clinically Significant, NCS=Not Clinically Significant 
 
Programming Note: If Flag is present (H, L, or AB), clinical significance will be identified by ‘NCS’ or ‘CS’. 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 72 of 84 
 
TesoRx Pharma, LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
 
Listing 16.2.8.4 
Clinical Laboratory Urinalysis – Positive Microscopic Findings  
 
 
 
 
 
 
Subject 
 
 
 
Period 
 
 
 
 
Treatment 
Visit 
Collection 
Date 
Collection 
Time 
Test Name 
Result 
Unit 
Flag 
Clinical 
Significance 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
H=High, L=Low, AB=Abnormal, CS=Clinically Significant, NCS=Not Clinically Significant 
 
Programming Note: If Flag is present (H, L, or AB), clinical significance will be identified by ‘NCS’ or ‘CS’. 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 73 of 84 
 
TesoRx Pharma, LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
 
 
Listing 16.2.8.5 
Clinical Laboratory Comments    
 
 
 
 
 
 
 
Subject 
 
 
 
Period 
Visit  
 
 
 
Collection 
Date 
Collection 
Time 
Lab Category 
Test Name 
Comment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lisitng only presents comments associated with our of range results for hematology, chemistry, or urinalysis lab tests.


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 74 of 84 
 
 
TesoRx Pharma, LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
Listing 16.2.8.6 
Other Clinical Laboratory Assessments - Testosterone Levels, PSA 
 
 
 
 
 
Subject 
 
 
 
Period 
 
 
 
 
 
Treatment Visit 
Collection 
Date  
 
 
 
 
Collection 
Time 
 
 
Lab 
Parameter 1 
(unit) 
Lab  
parameter 2 
(unit) 
 
 
 
 
 
 
Result/Flag 
Result/Flag 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
H=High, L=Low, AB=Abnormal, CS=Clinically Significant, NCS=Not Clinically Significant 
 
Programming Note: If Flag is present (H, L, or AB), clinical significance will be identified by ‘NCS’ or ‘CS’. 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 75 of 84 
 
TesoRx Pharma, LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
 
 
 
Listing 16.2.9.1 
Vital Signs – Observed Values  
 
 
 
 
 
 
Subject 
 
 
Period 
 
 
 
 
Treatment 
Visit 
 
 
 
Collection 
Date 
Collection 
Time 
 
Systolic Blood 
Pressure 
(mmHg) 
 
 
Diastolic 
Blood 
Pressure 
(mmHg) 
Heart Rate 
(beats/min) 
 
 
Respiratory 
Rate 
(breaths/min) 
 
 
Oral 
Temperature 
(0C) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 76 of 84 
 
TesoRx Pharma, LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
 
 
 
Listing 16.2.9.2 
Vital Signs – Change From Baseline  
 
 
 
 
 
 
 
Subject 
 
 
Period 
 
 
 
 
Treatment 
Visit 
 
 
 
Collection 
Date 
Collection 
Time 
 
Systolic Blood 
Pressure 
(mmHg) 
 
 
Diastolic 
Blood 
Pressure 
(mmHg) 
Heart Rate 
(beats/min) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 77 of 84 
 
  
TesoRx Pharma, LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
 
Listing 16.2.10.1 
12 Lead ECG Quantitative Findings 
  
 
 
 
 
 
 
Subject 
 
 
Period 
 
 
 
 
Treatment 
 
 
 
 
 
Visit 
 
 
 
 
 
Date 
 
 
 
 
 
Time  
Heart 
Rate 
(beats/ 
min 
PR 
 (msec) 
 
 
 
 
RR 
(msec) 
QRS  
(msec) 
 
 
 
 
QT  
(msec) 
QTcB 
 (msec) 
 
 
 
 
QTcF 
 (msec) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
QTcB = QT corrected according to Bazett, QTcF = QT corrected according to Fridericia. 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 78 of 84 
 
 
TesoRx Pharma, LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
 
Listing 16.2.10.2 
12 Lead ECG Quantitative Findings – Change From Baseline  
  
 
 
 
 
 
Subject 
 
 
Period 
 
 
 
 
Treatment 
 
 
 
 
 
 
 
 
Visit 
 
 
 
 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
Time  
 
 
 
 
 
 
 
QT  
 (msec) 
QTcB 
(msec) 
 
 
 
 
 
 
 
QTcF 
(msec) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
QTcB = QT corrected according to Bazett, QTcF = QT corrected according to Fridericia. 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 79 of 84 
 
 
TesoRx Pharma, LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
 
Listing 16.2.10.3 
12 Lead ECG – Qualitative Assessment  
 
 
 
 
 
 
 
Subject 
 
 
Period 
 
 
 
 
Treatment 
Visit 
Date 
Taken 
Time 
Taken 
Assessment 
Interpretation 
 
 
 
 
 
 
NORMAL 
 
 
 
 
 
 
 
ABNORMAL, NCS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NCS = Not Clinically Significant, CS = Clinically Significant 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 80 of 84 
 
TesoRx Pharma, LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
 
Listing 16.2.11 
Physical Examination Abnormal Findings  
 
 
 
 
 
 
 
Subject 
 
 
Period 
 
 
 
 
Treatment 
Visit 
Exam 
Date 
Exam 
Time 
Body System 
Abnormal 
Findings 
Clinical 
Significance 
 
 
 
 
 
 
 
 
NCS 
 
 
 
 
 
 
 
 
CS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NCS = Not Clinically Significant, CS = Clinically Significant 
 
  
 
 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 81 of 84 
 
TesoRx Pharma, LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
 
Listing 16.2.12.1 
QOL questionnaire - International Prostrate Symptom Score (IPSS) 
 
 
 
 
 
Subject 
Period 
 
 
 
 
Treatment 
Visit 
Date 
 
Time 
Symptom 
Result 
 
 
 
 
Score 
 
 
 
 
 
 
Incomplete emptying 
 
 
 
 
 
 
 
 
Frequency 
 
 
 
 
 
 
 
 
Intermittency 
 
 
 
 
 
 
 
 
Urgency 
 
 
 
 
 
 
 
 
Weak Stream 
 
 
 
 
 
 
 
 
Straining 
 
 
 
 
 
 
 
 
Nocturia 
 
 
 
 
 
 
 
 
Total 
 
 
 
 
 
 
 
 
QOL due to Urinary 
Symptoms 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programming note: ‘Result’ shows character score, ‘Score’ shows numeric


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 82 of 84 
 
TesoRx Pharma, LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
 
Listing 16.2.12.2 
QOL questionnaire – AMS  
 
 
 
 
 
Subject 
Period 
 
 
 
 
Treatment 
Visit 
Date 
 
Time 
Symptom 
Result 
 
 
 
 
Score 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programming note: ‘Result’ shows character score, ‘Score’ shows numeric 
 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 83 of 84 
 
TesoRx Pharma, LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
 
Listing 16.2.12.3 
QOL questionnaire – Male Sexual Dysfunction Multinational Survey of the Aging male (MSAM-7) 
 
 
 
 
 
Subject 
Period 
 
 
 
 
Treatment 
Visit 
Date 
 
Time 
Question 
Result 
 
 
 
 
Score 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programming note: ‘Result’ shows character score, ‘Score’ shows numeric 
 
 
 
 


PAREXEL International 
SAP Shells 
 
Final 1.0  
13 June 2018 
 
                                                                                                                                                                                                                Page 84 of 84 
 
TesoRx Pharma, LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page X of Y 
Protocol Number: TT-018 
 
 
Listing 16.2.12.4 
QOL questionnaire – Psychosexual Daily Questionnaire (PDQ) 
 
 
 
 
 
 
Subject 
Period 
 
 
 
 
Treatment 
Visit 
Date 
 
Time 
Question 
Result 
 
 
 
 
Score 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programming note: ‘Result’ shows character score, ‘Score’ shows numeric