A PHASE 1, OPEN-LABEL, RANDOMIZED, 2-TREATMENT SINGLE-DOSE, CROSS-OVER STUDY, 2-PART DESIGN TO EVALUATE THE BIOEQUIVALENCE AND TOLERABILITY OF TESTOSTERONE CYPIONATE FOLLOWING INTRAMUSCULAR (IM) INJECTION IN HEALTHY HYPOGONADAL MALE SUBJECTS
Phase: PHASE1
Conditions: Hypogonadism
Sponsor: Pfizer

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A PHASE 1, OPEN-LABEL, RANDOMIZED, 2-TREATMENT SINGLE-DOSE, 
CROSS-OVER STUDY, 2-PART DESIGN TO EVALUATE THE
BIOEQUIVALENCE AND TOLERABILITY OF TESTOSTERONE CYPIONATE
FOLLOWING INTRAMUSCULAR (IM) INJECTION IN HEALTHY
HYPOGONADAL MALE SUBJECTS
Investigational Product Number:
PF-03745638
Investigational Product Name:
Testosterone cypionate
United States (US) Investigational New 
Drug (IND) Number:
Not Applicable (N/A)
European Clinical Trials Database 
(EudraCT) Number:
Not Applicable (N/A)
Protocol Number:
B5341002
Phase:
1
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this information in
confidence and not copy or disclose it to others (except where required by applicable law) or use it for
unauthorized purposes.  In the event of any actual or suspected breach of this obligation, Pfizer must be promptly
notified.

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Document History
Document
Version Date
Summary of Changes and Rationale
Amendment #3
06 August 2019
•
Section 4.2 Screening supine systolic 
blood pressure 90-150 mm Hg
(inclusive) or diastolic blood pressure 
50-95 mm Hg (inclusive), following 
at least 5 minutes of supine rest.  If 
blood pressure is ≥150 mm Hg 
(systolic) or ≥95 mm Hg (diastolic), 
the BP should be repeated 2 more 
times and the average of the 3 BP
values should be used to determine 
the subject’s eligibility. Rationale:
More variability in the blood pressure 
in hypogonadal population.
Amendment #2
18 July 2019
•
Title changed to remove 2-Period. A 
corresponding change was also made 
in all applicable areas. Rationale: in 
Part 1, there are 2 periods and in 
Part 2, there are 3 periods.
 
 
 
 
 
 
 
•
Duration of subject participation 
Part 2 updated based on the new 
design (Protocol Summary, Section 3, 
Study design): each subject will 
participate in the study with the 
duration of approximately 25 weeks 
from the time the subject signs the 
informed consent form through the 
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Document
Version Date
Summary of Changes and Rationale
final contact/follow up contact.  This 
includes a screening phase up to 
4 weeks (28 days), ~16 weeks for 
dosing assuming, 45 days between 
treatments and up to 5 weeks for 
follow up contact.  
•
Addition of footnote “b” of SOA 
table to specify the updates applicable 
to only Part 2.
•
A window of no more than 2 hours is 
allowed (ie, 6-8 am) for sampling the 
predose samples.
•
Rationale: Language from Protocol 
Administrative Change Letter issued 
4th April 2019 included in Protocol 
Summary, SOA and Section 7.2.1.
•
Section 7.3 blood volume was 
updated to 306 mL. Rationale: Due 
to the addition of 3rd period 
additional blood samples will be 
collected for estimating testosterone 
and DHT.
•
Other typographical and editorial
errors were corrected throughout the 
document for clarity.
Amendment #1
11 Dec 2018
 
 
 
•
Addition of footnote “b” of SOA
table to specify baseline serum 
testosterone needed.  Rationale:
clarification for inclusion/exclusion 
criteria.
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Document
Version Date
Summary of Changes and Rationale
 
 
 
•
Change of hypogonadal male serum
testosterone from 300 ng/dL to 
250 ng/dL in Study rationale (1.3.1).
Rationale: Fix typographical error.
•
Change from Day 20 to Day 21 in 
SOA Table and Study overview (3.1). 
Rationale: to align with 480 hours.
 
 
 
•
A full physical exam will be 
performed in Period 2, Day -1 in
SOA table and.  “Limited” changed
to “full” in Subject Withdrawal (6.4).  
Rationale: Both changes to account 
for full physical for safety.
 
 
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Document
Version Date
Summary of Changes and Rationale
 
 
•
Addition of “PSA” in Safety
Laboratory Tests (Table 3) under 
“other.”  Rationale: add clarity and
synchronize with text.
•
Other typographical and editorial
errors were corrected throughout the 
document for clarity.
Original Protocol
15 May 2018
•
Not applicable (N/A).
This amendment incorporates all revisions to date, including amendments made at the request
of country health authorities and institutional review boards (IRBs)/ethics committees (ECs).
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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................9
APPENDICES ...........................................................................................................................9
PROTOCOL SUMMARY.......................................................................................................10
SCHEDULE OF ACTIVITIES................................................................................................13
1. INTRODUCTION ...............................................................................................................15
1.1. Mechanism of Action/Indication.............................................................................15
1.2. Background .............................................................................................................15
1.3. Rationale..................................................................................................................16
1.3.1. Study Rationale...........................................................................................16
1.3.2. Dose Rationale............................................................................................17
2. STUDY OBJECTIVES AND ENDPOINTS.......................................................................17
3. STUDY DESIGN.................................................................................................................18
3.1. Study Overview.......................................................................................................18
4. SUBJECT ELIGIBILITY CRITERIA.................................................................................20
4.1. Inclusion Criteria.....................................................................................................20
4.2. Exclusion Criteria....................................................................................................21
4.3. Lifestyle Requirements ...........................................................................................23
4.3.1. Meals and Dietary Restrictions...................................................................23
4.3.2. Alcohol, Caffeine, and Tobacco .................................................................23
4.3.3. Activity .......................................................................................................23
4.3.4. Contraception..............................................................................................24
4.4. Sponsor’s Qualified Medical Personnel..................................................................25
5. STUDY TREATMENTS.....................................................................................................25
5.1. Allocation to Treatment...........................................................................................25
5.2. Subject Compliance.................................................................................................26
5.3. Investigational Product Supplies.............................................................................26
5.3.1. Dosage Form and Packaging ......................................................................26
5.3.2. Preparation and Dispensing........................................................................26
5.4. Administration.........................................................................................................27
5.5. Investigational Product Storage...............................................................................27
5.6. Investigational Product Accountability...................................................................28

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5.6.1. Destruction of Investigational Product Supplies.........................................28
5.7. Concomitant Treatments .........................................................................................28
6. STUDY PROCEDURES .....................................................................................................29
6.1. Screening.................................................................................................................29
6.2. Study Period ............................................................................................................29
6.3. Follow-up ................................................................................................................30
6.3.1. Follow-up Contact ......................................................................................30
6.4. Subject Withdrawal.................................................................................................30
7. ASSESSMENTS..................................................................................................................32
7.1. Safety.......................................................................................................................32
7.1.1. Laboratory Tests .........................................................................................32
7.1.2. Physical Examinations................................................................................34
7.1.3. Blood Pressure (BP) and Pulse Rate...........................................................34
7.1.4. Electrocardiogram (ECG)...........................................................................34
7.2. Pharmacokinetics (PK)............................................................................................35
7.2.1. Serum for Analysis of Testosterone and Dihydrotestosterone ...................35
7.3. Blood Volume .........................................................................................................36
8. ADVERSE EVENT REPORTING......................................................................................36
8.1. Requirements...........................................................................................................36
8.1.1. Additional Details on Recording Adverse Events on the CRF...................37
8.1.2. Eliciting Adverse Event Information..........................................................37
8.1.3. Withdrawal From the Study Due to Adverse Events (see also the
Subject Withdrawal Section)...........................................................................37
8.1.4. Time Period for Collecting AE/SAE Information......................................38
8.1.4.1. Reporting SAEs to Pfizer Safety...............................................38
8.1.4.2. Recording Non-serious AEs and SAEs on the CRF..................38
8.1.5. Causality Assessment .................................................................................38
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities ..................39
8.2. Definitions...............................................................................................................39
8.2.1. Adverse Events ...........................................................................................39
8.2.2. Abnormal Test Findings .............................................................................40
8.2.3. Serious Adverse Events..............................................................................40

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8.2.4. Hospitalization............................................................................................41
8.3. Severity Assessment................................................................................................42
8.4. Special Situations ....................................................................................................42
8.4.1. Potential Cases of Drug-Induced Liver Injury............................................42
8.4.2. Exposure to the Investigational Product During Pregnancy or 
Breastfeeding, and Occupational Exposure.....................................................44
8.4.2.1. Exposure During Pregnancy......................................................44
8.4.2.2. Exposure During Breastfeeding ................................................45
8.4.2.3. Occupational Exposure .............................................................45
8.4.3. Medication Errors .......................................................................................46
8.4.3.1. Medication Errors......................................................................46
9. DATA ANALYSIS/STATISTICAL METHODS...............................................................47
9.1. Sample Size Determination.....................................................................................47
9.2. Efficacy Analysis ....................................................................................................47
9.3. Pharmacokinetic Analysis.......................................................................................47
9.3.1. Derivation of Pharmacokinetic Parameters Prior to Analysis ....................47
9.3.2. Analysis Populations ..................................................................................48
9.3.3. Statistical Analyses of Pharmacokinetic Parameters..................................48
9.5. Interim Analysis ......................................................................................................50
10. QUALITY CONTROL AND QUALITY ASSURANCE.................................................50
11. DATA HANDLING AND RECORD KEEPING .............................................................51
11.1. Case Report Forms/Electronic Data Record .........................................................51
11.2. Record Retention...................................................................................................52
12. ETHICS..............................................................................................................................52
12.1. Institutional Review Board/Ethics Committee......................................................52
12.2. Ethical Conduct of the Study ................................................................................52
12.3. Subject Information and Consent..........................................................................53
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP ...........................................................................................................................54
13. DEFINITION OF END OF TRIAL...................................................................................54
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13.1. End of Trial in the United States ...........................................................................54
14. SPONSOR DISCONTINUATION CRITERIA ................................................................54
15. PUBLICATION OF STUDY RESULTS ..........................................................................54
15.1. Communication of Results by Pfizer.....................................................................54
15.2. Publication by Investigators..................................................................................55
16. REFERENCES ..................................................................................................................57
LIST OF TABLES
Table 1.
Schedule of Activities...............................................................................13
Table 2.
Study Schematics......................................................................................19
Table 3.
Safety Laboratory Tests............................................................................33
Table 4.
Derivation of Pharmacokinetic Parameters ..............................................48
Table 5.
Safety QTc Assessment ............................................................................50
APPENDICES
Appendix 1. Abbreviations......................................................................................................58

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PROTOCOL SUMMARY
The current presentation of testosterone cypionate solution for injection is highly
concentrated (supersaturation) with respect to the active pharmaceutical ingredient (API) and 
therefore makes the product susceptible to crystallization when exposed to lower
temperatures than recommended on the approved label [20°C to 25°C (68°F to 77°F)].  
Currently the 200 mg/mL United States Prescribing Information1 (USPI) include “Warming
and shaking the vial should re-dissolve any crystals that may have formed during storage at
temperatures lower than recommended”.  To avoid crystallization and maintain true solution
properties, the 200 mg/mL formulation is being modified to improve the solubility of the
active ingredient in the vehicle.  The current study will be assessing the bioequivalence (BE)
and tolerability between the currently approved formulation and the reformulated 
presentation of testosterone cypionate solution for injection.
This is an open-label, randomized, 2-treatment, single-dose, cross-over study, 2-part design 
to evaluate the BE and tolerability of testosterone cypionate solution for intramuscular (IM)
injection in healthy hypogonadal male subjects (ages of 18 to 65 years).
The objectives and endpoints of this study are listed below.
Part 1
Primary Objective:
Primary Endpoints:
•
To estimate the exposure variability of the
test and reference formulations of
testosterone cypionate solution for
injection (200 mg) given intramuscularly
as a single dose.
•
AUClast, AUCinf, and Cmax of total
testosterone (baseline corrected).
 
 
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Part 2
Primary Objective:
Primary Endpoint(s):
•
To evaluate the BE of the new formulation
(testosterone cypionate solution for 
injection; 200 mg) relative to the currently
marketed formulation (testosterone
cypionate solution for injection; 200 mg) 
administered intramuscularly as a single 
dose.
•
AUClast, AUCinf (if data permit), and Cmax
of total testosterone (baseline corrected).
 
In Part 1, approximately 12 subjects will be enrolled to ensure 10 evaluable subjects in the
study.  Subjects will be randomized according to a computer-generated randomization
schedule to receive the following 2 treatments below in random order.
Treatment A:
A single testosterone cypionate solution for injection (new formulation) 200 mg dose
administered IM deep in the gluteal muscle (Test formulation).
Treatment B:
A single testosterone cypionate solution for injection (currently marketed formulation)
200 mg dose administered IM deep in the gluteal muscle (Reference formulation).
In Part 2, approximately 60 subjects will be enrolled to ensure 57 evaluable subjects in the 
study. In Part 2, the variability associated with maximum observed concentration (Cmax) and 
area under the curve (AUC) as well as the point estimates obtained from Part 1 were to be 
used to inform the sample size needed to attain BE.
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Subjects will be randomized according to a computer-generated randomization schedule to
receive the 2 treatments (eg, same as listed in Part 1) in a random order.
For Part 1, each subject will participate in the study with the duration of approximately
19 weeks from the time the subject signs the informed consent form through the final 
contact/follow-up contact. This includes a screening phase up to 4 weeks (28 days), 
~10 weeks for dosing assuming, 45 days between treatments and up to 5 weeks for follow-up
contact.
For Part 2, each subject will participate in the study with the duration of approximately 
25 weeks from the time the subject signs the informed consent form through the final 
contact/follow-up contact.  This includes a screening phase up to 4 weeks (28 days), 
~16 weeks for dosing assuming, 45 days between treatments and up to 5 weeks for follow-up 
contact.  
For each Part separately, natural log transformed area under the plasma concentration-time
profile from time 0 to the time of the last quantifiable concentration (AUClast), area under the
plasma concentration-time profile from time zero extrapolated to infinite time (AUCinf) (if
data permit) and Cmax of total testosterone (baseline corrected [mean of the 4 predose
measurements] and uncorrected) will be analyzed separately using a mixed effect model with
sequence, period and treatment as fixed effects and subject within sequence as a random
effect. Estimates of the adjusted mean differences (Test – Reference) and corresponding
90% confidence intervals will be obtained from the model. The adjusted mean differences 
and 90% confidence intervals for the differences will be exponentiated to provide estimates of 
the ratio of adjusted geometric means (Test/Reference) and 90% confidence intervals for the 
ratios.
For each Part separately, pharmacokinetic (PK) concentrations and parameters will be listed,
summarized descriptively and graphed per sponsor standards.
If results from Part 1 depict within-subject variability ≥30% (eg, highly variable drug), the
study design and/or methodology of data analysis may be modified.

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SCHEDULE OF ACTIVITIES
The schedule of activities table provides an overview of the protocol visits and procedures. Refer to the STUDY PROCEDURES and
ASSESSMENTS sections of the protocol for detailed information on each procedure and assessment required for compliance with the
protocol.
The investigator may schedule visits (unplanned visits) in addition to those listed in the schedule of activities table, in order to conduct
evaluations or assessments required to protect the well-being of the subject.
Table 1.
Schedule of Activities
Visit Identifiera
Screen
Periods 123b (45 day washout in between drug administration)
Day -1
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6 Day 7 Day 8
Day 
11
Day 
15
Day 
21
Follow-up*
Hours Post Dose
-1
-0.5
-0.25
0
1
8
24
36
48
72
96
120
144
168
240
336
480
Informed consent
X
CRU confinement
X
→
→
→
→
→
→
→
X
Inclusion/exclusion 
criteriac
X
X
Medical history
X
X
Alcohol breath test or 
alcohol blood testd
X
Physical examination
X
Xe
Xf
Safety laboratory
X
X
Demography
X
Height and weight
X
Contraception checkg
X
X
X
→
→
→
→
→
→
→
X
Urine drug testing
X
X
PSA test and rectal 
examination
X
X
ECG
X
X
X
BP and pulse rate
X
X
HIV, HepBsAg, 
HepBcAb, HCVAb 
testing
X
Study treatment 
administration
X
PK blood sampling
Xh
Xh
Xh
Xh
X
X
X
X
X
X
X
X
X
X
X
X
X

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Visit Identifiera
Screen
Periods 123b (45 day washout in between drug administration)
Day -1
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6 Day 7 Day 8
Day 
11
Day 
15
Day 
21
Follow-up*
Hours Post Dose
-1
-0.5
-0.25
0
1
8
24
36
48
72
96
120
144
168
240
336
480
Serious and
non-serious AE 
monitoring
X
X
X ----------------------------------------------------------------------------------------------------------------------------------------------
X
Prior and concomitant 
treatment(s)
X
X
X
→
→
→
→
→
→
→
→
→
X
CRU dischargei
X
Abbreviations: →= ongoing/continuous event; AE = adverse event(s); BP = blood pressure; CRU = clinical research unit; ECG = electrocardiogram;
HCVAb = hepatitis C antibody; HepBcAb = hepatitis B core antibody; HepBsAg = hepatitis B surface antigen; HIV = human immunodeficiency virus;
PK = pharmacokinetic; PSA = Prostate Specific Antigen.
a.
Day relative to start of study treatment (Day 1).
b.
Part 2 only.
c.
For inclusion into the study, one sample resulting in a serum testosterone of <250 ng/dL must be confirmed.
d.
Performed at the discretion of the investigator.
e.
A full exam will be performed at Day -1 for Period 1 if deferred from previous screening visit; A limited physical exam to be undertaken at Day -1 if full 
exam already performed at previous screening visit. A full physical exam will be performed in Period 2, Day -1.
f.
A full physical exam will be performed at Part 2 Period 3 Day 21 only or upon study discontinuation.
g.
The investigator must assess and document in the source if the subject is biologically capable of having children and if the subject continues to be or has 
become sexually active.  If yes, their method of contraception and confirmation of its consistent and correct use must also be documented in the source 
documents.
h.
Four pre-dose samples will be collected at -1, -0.5, -0.25, and 0 hours to determine endogenous levels of baseline testosterone. Samples should be collected 
between 7 and 8 am if dosing occurs for example at 8 am (recommended). A window of no more than 2 hours is allowed (ie, 6-8 am).
i.
Subjects may remain at the CRU for longer period of time at the discretion of the investigator.
* A follow-up contact with the subject must be scheduled at the end of the AE/SAE active collection period. See the Follow-up section (Section 6.3).

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1. INTRODUCTION
The current presentation of testosterone cypionate solution for injection (200 ng/mL) is 
highly concentrated (supersaturation) with respect to the active API and therefore makes the
product susceptible to crystallization when exposed to lower temperatures than recommended 
on the approved label [20°C to 25°C (68°F to 77°F)].  Currently the product USPI1 includes 
“Warming and shaking the vial should re-dissolve any crystals that may have formed during 
storage at temperatures lower than recommended”.  To avoid crystallization and maintain
true solution properties, the 200 mg/mL formulation is being modified to improve the 
solubility of the active ingredient in the vehicle, via an increase in the concentration of 
benzyl benzoate from 20% to 30% and a commensurate reduction in cottonseed oil from
560 mg to 470 mg to maintain mass balance. The current study will be assessing the BE and 
tolerability between the currently approved formulation and the reformulated presentation of 
testosterone cypionate solution for injection.
1.1. Mechanism of Action/Indication
Testosterone cypionate solution for injection is indicated for replacement therapy in males in
conditions associated with symptoms of deficiency or absence of endogenous testosterone.1

Primary hypogonadism (congenital or acquired)-testicular failure due to
cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome; or
orchidectomy.

Hypogonadotropic hypogonadism (congenital or acquired)-idiopathic gonadotropin or
Luteinizing Hormone Releasing Hormone (LHRH) deficiency, or
pituitary-hypothalamic injury from tumors, trauma, or radiation.
1.2. Background
Endogenous androgens are responsible for normal growth and development of the male sex
organs and for maintenance of secondary sex characteristics.1  These effects include growth
and maturation of the prostate, seminal vesicles, penis, and scrotum, development of male
hair distribution, such as beard, pubic, chest, and axillary hair, laryngeal enlargement, vocal
cord thickening, and alterations in body musculature and fat distribution. Drugs in this class 
also cause retention of nitrogen, sodium, potassium, and phosphorous, and decreased urinary
excretion of calcium.  Androgens have been reported to increase protein anabolism and 
decrease protein catabolism.  Nitrogen balance is improved only when there is sufficient 
intake of calories and protein.
During exogenous administration of androgens, endogenous testosterone release is inhibited 
through feedback inhibition of pituitary luteinizing hormone (LH). At large doses of 
exogenous androgens, spermatogenesis may also be suppressed through feedback inhibition
of pituitary follicle-stimulating hormone (FSH).  There is a lack of substantial evidence that 
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Testosterone esters are less polar than free testosterone. Testosterone esters in oil when
injected intramuscularly are absorbed slowly from the lipid phase; thus, testosterone
cypionate solution for injection can be given at intervals of 2 to 4 weeks.
Following IM administration in an oily vehicle, testosterone ester is slowly absorbed into the
general circulation and then rapidly hydrolysed in plasma to testosterone. In a randomized
cross-over study of 6 healthy males, the PK of a single injection of 200 mg testosterone
cypionate was compared to that of a single injection of 194 mg testosterone enanthate. Mean
serum testosterone concentrations increased to 3 times the basal levels at 24 hours and 
declined gradually to basal levels by Day 10. Testosterone in plasma is 98% bound to a
specific testosterone-estradiol binding globulin, and about 2% is free. About 90% of a dose
of testosterone is excreted in the urine as glucuronic and sulfuric acid conjugates of 
testosterone and its metabolites; about 6% of a dose is excreted in the feces, mostly in the 
unconjugated form.  Inactivation of testosterone occurs primarily in the liver.  Testosterone is 
metabolized to various 17-keto steroids through 2 different pathways. The half-life of
testosterone cypionate when injected intramuscularly is approximately 8 days.  Testosterone
cypionate for IM injection is currently approved for testosterone replacement therapy in
hypogonadal men.
Prolonged use of high doses of androgens has been associated with the development of 
hepatic adenomas, hepatocellular carcinoma, and peliosis hepatis, all potentially
life-threatening complications.  Long-term clinical safety trials have not been conducted to 
assess the cardiovascular outcomes of testosterone replacement therapy in men. To date, 
epidemiologic studies and randomized controlled trials have been inconclusive for 
determining the risk of major adverse cardiovascular events (MACE).  Some studies, but not 
all, have reported an increased risk of MACE in association with use of testosterone 
replacement therapy in men. Patients should be informed of this possible risk when deciding 
whether to use or to continue to use DEPO-Testosterone (testosterone cypionate).  
Testosterone has been subject to abuse, typically at doses higher than recommended for the 
approved indication and in combination with other anabolic androgenic steroids.  Edema, 
with or without congestive heart failure, may be a serious complication in patients with
pre-existing cardiac, renal or hepatic disease.  Gynecomastia may develop and occasionally 
persist in patients being treated for hypogonadism.
Additional information for this compound may be found in the single reference safety
document, which for this study is the Depo-Testosterone USPI.1
1.3. Rationale
1.3.1. Study Rationale
The current study will be assessing the BE between the current formulation (Reference
formulation) and the reformulated presentation of testosterone cypionate injection (Test
formulation) at a single 200 mg IM dose administered deep in the gluteal muscle. Since
endogenous testosterone can interfere with the interpretation of systemic testosterone levels,
the study will be conducted in hypogonadal males defined as subjects having serum
testosterone levels below 2.5 ng/mL (250 ng/dL). Overall, the study design incorporates

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2 parts.  As the variability associated with the PK of the reformulated presentation of 
testosterone cypionate solution for injection is unknown, Part 1 will assess the variability
associated with exposures after administration of both the current formulation and
reformulated presentation of testosterone cypionate solution for injection. Part 2 will
evaluate the BE between both test and reference treatments.
 
 
 
 
 
 
 
 
 
  
1.3.2. Dose Rationale
Testosterone cypionate solution for intramuscular injection is currently approved for
testosterone replacement therapy in hypogonadal men. Testosterone cypionate solution for
injection is available as 100 mg/mL strength (in 10 mL vials) and in 200 mg/mL strength (in
1 and 10 mL vials).  The suggested dosage for testosterone cypionate solution for injection
varies depending on the age, sex, and diagnosis of the individual patient. Dosage is adjusted
according to the patient’s response and the appearance of adverse reactions.  For testosterone 
replacement therapy in the hypogonadal male, it is recommended that 50-400 mg should be
administered every 2 to 4 weeks (per the USPI).1  A 200 mg dose is selected for this study as
the recommended dose in the drug label for hypogonadal males is 200 mg administered IM
every 2 weeks (USPI).1
2. STUDY OBJECTIVES AND ENDPOINTS
Part 1
Primary Objective:
Primary Endpoints:
•
To estimate the exposure variability of the
test and reference formulations of
testosterone cypionate solution for
injection (200 mg) given intramuscularly
as a single dose.
•
AUClast, AUCinf and Cmax of total
testosterone (baseline corrected).
 
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•
Part 2
Primary Objective:
Primary Endpoints:
•
To evaluate the BE of the new formulation 
(testosterone cypionate solution for 
injection; 200 mg) relative to the currently
marketed formulation (testosterone 
cypionate solution for injection; 200 mg) 
administered intramuscularly as a single 
dose.
•
AUClast, AUCinf (if data permit), and Cmax
of total testosterone (baseline corrected).
 
3. STUDY DESIGN
3.1. Study Overview
This is an open-label, randomized, 2-treatment, single-dose, cross-over study, 2-part design 
to evaluate the BE and tolerability of testosterone cypionate solution for injection (IM) 
administration in healthy hypogonadal male subjects (ages of 18 to 65 years). In Part 1, 
approximately 12 subjects will be enrolled in the study to ensure 10 evaluable subjects are to 
be randomized according to a computer-generated randomization schedule to receive the 
following 2 treatments below in random order.
Treatment A: A single testosterone cypionate solution for injection (new formulation)
200 mg dose administered IM deep in the gluteal muscle (Test).
CCI
CCI

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Treatment B: A single testosterone cypionate solution for injection (currently marketed
formulation) 200 mg dose administered IM deep in the gluteal muscle (Reference).
In Part 2, the observed variability associated with Cmax and AUC as well as the point 
estimates obtained from Part 1, were used to estimate the sample size needed to attain 
bioequivalence (BE) in Part 2. In Part 2, it is anticipated that approximately 60 subjects will 
be enrolled to ensure 57 evaluable subjects. Subjects will be randomized according to a 
computer-generated randomization schedule to receive the 2 treatments (eg, same as listed in 
Part 1) in a random order.
As results from Part 1 demonstrated within-subject variability ≥30% (eg, highly variable 
drug) with respect to baseline corrected testosterone PK parameters, the study design and 
methodology for data analysis of Part 2 has been modified to a partial replicate design.
Table 2.
Study Schematics
Part 1 (12 subjectsa)
Sequence
Period 1
Washout Period
Period 2
1
(6 subjects)
Test treatment
At least 45 days
Reference treatment
2
(6 subjects)
Reference treatment
Test treatment
Part 2 (60 subjectsb)
Sequence
Period 1
Washout Period
Period 2
Washout Period
Period 3
1
(20 subjects)
Test treatment
At least 45 days
Reference
treatment
At least 45 days
Reference
treatment
2
(20 subjects)
Reference
treatment
Test treatment
Reference 
treatment
3
(20 subjects)
Reference
treatment
Reference 
treatment
Test treatment
a.
In Part 1, approximately 12 subjects will be enrolled to ensure 10 evaluable subjects.
b.
In Part 2, approximately 60 subjects will be enrolled to ensure 57 evaluable subjects.
Screening evaluation will occur within 28 days prior to the first dose of study medication.
Day -1 is defined as the day prior to first day of dosing (Day 1) for each study treatment. 
Subjects will be admitted to the Clinical Research Unit (CRU) on Day -1 and will remain at
the CRU on Days 1-2 following administration of study medication. Subjects will be asked
to return to the clinic for each subsequent PK sampling through Day 21. Subjects may
remain at the CRU for a longer period of time at the discretion of the investigator. The
baseline endogenous testosterone level will be the mean of four (4) pre-dose PK samples
collected at -1.0, -0.5, -0.25 and 0 hours so that an average baseline correction of endogenous
total testosterone levels can be calculated. These 4 pre-dose samples should be collected
between the hours of 07:00 and 08:00 AM on the day of study drug administration, if dosing 
occurs for example at 8 am (recommended). A window of no more than 2 hours is allowed 
(ie, 6-8 am).

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On Day 1, subjects will receive a single IM dose of either Test or Reference treatment
according to randomization code.  There will be at least a 45-day washout period between
administration of each study medication in both Parts 1 and 2.
Blood samples (6 mL each) will be collected prior to dosing (-1.0, -0.5, -0.25, and 0) and at
1, 8, 24, 36, 48, 72, 96, 120, 144, 168, 240, 336, and 480 hours post-dose for analysis of total
testosterone (free and protein bound) and its metabolite, dihydrotestosterone (DHT).
Tolerability and safety will be assessed for all treatments by monitoring adverse events 
(AE) s.
For Part 1, each subject will participate in the study with the duration of approximately 
19 weeks from the time the subject signs the informed consent form through the final 
contact/follow-up contact. This includes a screening phase up to 4 weeks (28 days), 
~10 weeks for dosing assuming, 45 days between treatments and up to 5 weeks for follow-up 
contact. 
For Part 2, each subject will participate in the study with the duration of approximately 
25 weeks from the time the subject signs the informed consent form through the final 
contact/follow-up contact.  This includes a screening phase up to 4 weeks (28 days), 
assuming ~16 weeks for dosing, 45 days between treatments and up to 5 weeks for follow-up 
contact.  
4. SUBJECT ELIGIBILITY CRITERIA
This study can fulfill its objectives only if appropriate subjects are enrolled.  The following 
eligibility criteria are designed to select subjects for whom participation in the study is 
considered appropriate.  All relevant medical and nonmedical conditions should be taken into 
consideration when deciding whether a particular subject is suitable for this protocol.
4.1. Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for enrollment in the
study:
1. Hypogonadal male subjects who, at the time of screening, are otherwise healthy and
between the ages of 18 and 65 years, inclusive.  Healthy is defined as no clinically
relevant abnormalities identified by a detailed medical history, full physical
examination, including blood pressure (BP) and pulse rate measurement, 12-lead
electrocardiogram (ECG), or clinical laboratory tests.
Hypogonadism is defined as serum testosterone level below 2.5 ng/mL (250 ng/dL).
2. Body mass index (BMI) of 17.5 to 35 kg/m2; and a total body weight >50 kg 
(110 lb).
3. Evidence of a personally signed and dated informed consent document indicating that 
the subject has been informed of all pertinent aspects of the study.

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4. Subjects who are willing and able to comply with all scheduled visits, treatment plan,
laboratory tests, and other study procedures.
4.2. Exclusion Criteria
Subjects with any of the following characteristics/conditions will not be included in the 
study:
1. Evidence or history of clinically significant hematological, renal, endocrine, 
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or
allergic disease (including drug allergies, but excluding untreated, asymptomatic,
seasonal allergies at the time of dosing).
2. Subjects who are currently being treated for hypogonadism. This is defined as 
patients who have received a testosterone injectable product within the past 3 months 
or have used a transdermal or gel product within the past 2 weeks.
3. A positive urine drug test.
4. History of regular alcohol consumption exceeding 14 drinks/week (1 drink = 5 ounces
[150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard
liquor) within 6 months before screening.
5. Treatment with an investigational drug within 30 days (or as determined by the local
requirement) or 5 half-lives preceding the first dose of investigational product
(whichever is longer).
6. Screening supine systolic BP 90-150 mm Hg (inclusive) or diastolic BP 50-95 mm 
Hg (inclusive), following at least 5 minutes of supine rest.  If BP is ≥150 mm Hg 
(systolic) or ≥95 mm Hg (diastolic), the BP should be repeated 2 more times and the 
average of the 3 BP values should be used to determine the subject’s eligibility.
7. Screening supine 12-lead ECG demonstrating a corrected QT (QTc) interval
>450 msec or a QRS interval >120 msec. If QTc exceeds 450 msec, or QRS exceeds
120 msec, the ECG should be repeated 2 more times and the average of the 3 QTc or
QRS values should be used to determine the subject’s eligibility.
8. Subjects with ANY of the following abnormalities in clinical laboratory tests at 
screening, as assessed by the study-specific laboratory and confirmed by a single 
repeat test, if deemed necessary:

Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level
≥3 × upper limit of normal (ULN);

Total bilirubin level ≥1.5 × ULN; subject with a history of Gilbert’s syndrome
may have direct bilirubin measured and would be eligible for this study provided
the direct bilirubin level is ≤ULN.

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9. Fertile male subjects who are unwilling or unable to use a highly effective method of 
contraception as outlined in this protocol [Contraception (Section 4.3.4)] for the 
duration of the study and for at least 45 days after the last dose of investigational 
product.
10. Use of prescription or nonprescription drugs and dietary supplements within 7 days or
5 half-lives (whichever is longer) prior to the first dose of investigational product. As
an exception, acetaminophen/paracetamol may be used at doses of ≤1 g/day. Limited
use of nonprescription medications that are not believed to affect subject safety or the 
overall results of the study may be permitted on a case-by-case basis following
approval by the sponsor.
11. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or 
more within 56 days prior to dosing.
12. History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; positive 
testing for HIV, hepatitis B surface antigen (HepBsAg), hepatitis B core antibody
(HepBcAb), or hepatitis C antibody (HCVAb).
13. History of sensitivity to heparin or heparin-induced thrombocytopenia.
14. Unwilling or unable to comply with the criteria in the Lifestyle Requirements section 
of this protocol.
15. Subjects who are investigator site staff members directly involved in the conduct of
the study and their family members, site staff members otherwise supervised by the
investigator, or subjects who are Pfizer employees, including their family members,
directly involved in the conduct of the study.
16. Other acute or chronic medical or psychiatric condition including recent (within the
past year) or active suicidal ideation or behavior or laboratory abnormality that may
increase the risk associated with study participation or investigational product 
administration or may interfere with the interpretation of study results and, in the 
judgment of the investigator, would make the subject inappropriate for entry into this
study.
17. Subjects with carcinoma of the breast.
18. Subjects with known or suspected carcinoma of the prostate gland.
19. Subjects who are hypersensitive to testosterone cypionate or its inactive ingredients.

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4.3. Lifestyle Requirements
The following guidelines are provided:
4.3.1. Meals and Dietary Restrictions

Subjects must abstain from all food and drink (except water) at least 4 hours prior to 
any safety laboratory evaluations and 10 hours prior to the collection of the predose
PK sample. Water is permitted until 1 hour prior to investigational product
administration.

Water may be consumed without restriction beginning 1 hour after dosing.

Non-caffeinated drinks (except grapefruit or grapefruit-related citrus fruit juices, see
below) may be consumed with meals and the evening snack.

Lunch will be provided approximately 4 hours after dosing.

Dinner will be provided approximately 9 to 10 hours after dosing.

An evening snack may be permitted.

While confined, the total daily nutritional composition should be approximately 
55% carbohydrate, 30% fat, and 15% protein.  The daily caloric intake per subject
should not exceed approximately 3200 kcal.
4.3.2. Alcohol, Caffeine, and Tobacco

Subjects will abstain from alcohol for 24 hours prior to admission to the CRU and
continue abstaining from alcohol until collection of the final PK sample of each study
period.  Subjects may undergo an alcohol breath test or blood alcohol test at the
discretion of the investigator.

Subjects will abstain from caffeine-containing products for 24 hours prior to the start
of dosing until collection of the final PK sample of each study period.

Subjects will abstain from the use of tobacco- or nicotine-containing products for
24 hours prior to dosing and during confinement in the CRU.
4.3.3. Activity
Subjects will abstain from strenuous exercise (eg, heavy lifting, weight training, calisthenics,
aerobics) for at least 48 hours prior to each blood collection for clinical laboratory tests.  
Walking at a normal pace will be permitted.

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4.3.4. Contraception
All fertile male subjects, who are, in the opinion of the investigator, sexually active and at
risk for pregnancy with their partner(s) must agree to use a highly effective method of 
contraception consistently and correctly for the duration of the active treatment period and for 
at least 45 days after the last dose of investigational product.  The investigator or his or her
designee, in consultation with the subject, will confirm that the subject has selected an
appropriate method of contraception for the individual subject and his or partner(s) from the
permitted list of contraception methods (see below) and will confirm that the subject has
been instructed in its consistent and correct use. At time points indicated in the Schedule of 
Activities, the investigator or designee will inform the subject of the need to use highly
effective contraception consistently and correctly and document the conversation and the
subject’s affirmation in the subject’s chart (subjects need to affirm their consistent and
correct use of at least 1 of the selected methods of contraception).  In addition, the
investigator or designee will instruct the subject to call immediately if the selected 
contraception method is discontinued or if pregnancy is known or suspected in the partner.
Highly effective methods of contraception are those that, alone or in combination, result in a
failure rate of less than 1% per year when used consistently and correctly (ie, perfect use) and
include the following:

Correctly placed copper-containing intrauterine device (IUD).

Male condom or female condom used WITH a separate spermicide product (ie, foam,
gel, film, cream, or suppository). For countries where spermicide is not available or
condom plus spermicide is not accepted as highly effective contraception, this option
is not appropriate.

Male sterilization with absence of sperm in the postvasectomy ejaculate.

Bilateral tubal ligation/bilateral salpingectomy or bilateral tubal occlusive procedure
(provided that occlusion has been confirmed in accordance with the device’s label).
NOTE: Sexual abstinence, defined as completely and persistently refraining from all 
heterosexual intercourse (including during the entire period of risk associated with the study 
treatments) may obviate the need for contraception ONLY if this is the preferred and usual 
lifestyle of the subject.
All sexually active male subjects must agree to prevent potential transfer to and exposure of 
partner(s) to drug through ejaculate by using a condom consistently and correctly, beginning 
with the first dose of investigational product and continuing for at least 45 days after the last 
dose of testosterone cypionate.

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4.4. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the study supporting documentation.
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, subjects are provided with a contact card. The contact card contains, 
at a minimum, protocol and investigational product identifiers, subject study numbers, 
contact information for the investigator site, and contact details for a contact center in the 
event that the investigator site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
subject’s participation in the study.  The contact number can also be used by investigator 
staff if they are seeking advice on medical questions or problems; however, it should be used 
only in the event that the established communication pathways between the investigator site 
and the study team are not available.  It is therefore intended to augment, but not replace, the 
established communication pathways between the investigator site and the study team for
advice on medical questions or problems that may arise during the study. For sites other than 
a Pfizer CRU, the contact number is not intended for use by the subject directly, and if a 
subject calls that number, he or she will be directed back to the investigator site.
5. STUDY TREATMENTS
For the purposes of this study, and per International Conference on Harmonisation (ICH)
guidelines, investigational product is defined as a pharmaceutical form of an active
ingredient or placebo being tested or used as a reference/comparator in a clinical trial,
including a product with a marketing authorization when used or assembled (formulated or
packaged) in a way different from the approved form, or when used for an unapproved 
indication, or when used to gain further information about an approved use (ICH E6 1.33).
For this study, the investigational products are:

Testosterone Cypionate Solution for Injection 200 mg/mL (Test);

Testosterone Cypionate Solution for Injection 200 mg/mL (Reference).
5.1. Allocation to Treatment
The investigator’s knowledge of the treatment should not influence the decision to enroll a 
particular subject or affect the order in which subjects are enrolled.
The investigator will assign subject numbers to the subjects as they are screened for the 
study.  Pfizer will provide a randomization schedule to the investigator and, in accordance 
with the randomization numbers, the subject will receive the study treatment regimen 
assigned to the corresponding randomization number.

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5.2. Subject Compliance
Investigational product will be administered under the supervision of investigator site 
personnel.
For Part 1, Subjects will be admitted to the CRU on Day -1 of Periods 1 and 2, will remain at 
the CRU on Days 1-2 during those periods and will be supervised by the site staff.  
For Part 2, Subjects will be admitted to the CRU on Day -1 of Periods 1, 2 and 3, will remain 
at the CRU on Days 1-2 during those periods and will be supervised by the site staff.  
Subjects may remain at the CRU for a longer period of time at the discretion of the 
investigator.
Treatment compliance will be ensured by the following procedures:

For each subject, all doses of the study drug will be administered per the timing 
described in the protocol Schedule of Activities and by the appropriately designated
study staff at the CRU.

Study drug administration will be recorded in the source documents and entered in the 
appropriate section of the case report form (CRF). Any problems with the injection 
will be recorded in the source documents and in the CRFs.
5.3. Investigational Product Supplies
5.3.1. Dosage Form and Packaging
Testosterone cypionate solution for injection 200 mg/mL sterile vials will be supplied to the
CRU by Pfizer as packaged Single Dose Vial (SDV) and labeled according to local
regulatory requirements.  Each SDV and the outer carton will contain a single panel label and
will be provided in Open-Label fashion. The vials will be provided to the site for dispensing
by the pharmacy.
Pivotal BE retain vials will be supplied to the CRU in individual labeled containers (in
sufficient number to allow unopened containers to be kept as retains).
5.3.2. Preparation and Dispensing
Within this protocol, preparation refers to the investigator site activities performed to make
the investigational product ready for administration or dispensing to the subject/caregiver by
qualified staff.  Dispensing is defined as the provision of investigational product, 
concomitant treatments, and accompanying information by qualified staff member(s) to a
healthcare provider, subject, or caregiver in accordance with this protocol.  Local health
authority regulations or investigator site guidelines may use alternative terms for these 
activities.

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See the Investigational Product (IP) Manual for instructions on how to prepare the
investigational product for administration. Investigational product should be prepared and
dispensed by an appropriately qualified and experienced member of the study staff (eg,
physician, nurse, physician’s assistant, nurse practitioner, pharmacy assistant/technician, or
pharmacist) as allowed by local, state, and institutional guidance.
5.4. Administration
Dosing will be administered on Day 1 of each Study Period by qualified medical personnel. 
The time of each drug administration will be recorded to the nearest minute.
The dose of testosterone cypionate (eg, investigational product) to be administered in this 
study is 200 mg in 1 mL solution.  Each subject will receive either 200 mg of testosterone 
cypionate (Test) or 200 mg of testosterone cypionate (Reference) as a single IM dose in a 
particular treatment period. The investigation product will be administered according to the 
IP Manual. Each dose of study drug will be administered as an IM injection deep in the 
gluteal muscle in the same region for both periods.
In order to standardize the conditions on PK sampling days, all subjects will be required to 
refrain from lying down (except when required for BP, pulse rate, and ECG measurements), 
eating, and drinking beverages other than water during the first 4 hours after dosing.
5.5. Investigational Product Storage
The investigator or an approved representative, eg, pharmacist, will ensure that all 
investigational products are stored in a secured area with controlled access under required 
storage conditions and in accordance with applicable regulatory requirements.
Investigational products should be stored in their original containers and in accordance with 
the labels.
Any storage conditions stated in the single reference safety document (SRSD) will be 
superseded by the storage conditions stated on the product label.
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations (as 
applicable, including frozen, refrigerated, and/or room-temperature products). This should 
be captured from the time of investigational product receipt throughout the study. Even for 
continuous-monitoring systems, a log or site procedure that ensures active evaluation for 
excursions should be available.  The intent is to ensure that the minimum and maximum
temperature is checked each business day to confirm that no excursion occurred since the last 
evaluation and to provide the site with the capability to store or view the minimum/maximum 
temperature for all non-working days upon return to normal operations.  The operation of the 
temperature-monitoring device and storage unit (for example, refrigerator), as applicable, 
should be regularly inspected to ensure they are maintained in working order.

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Any excursions from the product-label storage conditions should be reported to Pfizer upon 
discovery.  The site should actively pursue options for returning the product to the storage 
conditions described in the labeling, as soon as possible.  Deviations from the storage 
requirements, including any actions taken, must be documented and reported to Pfizer.
Once an excursion is identified, the investigational product must be quarantined and not used 
until Pfizer provides permission to use the investigational product.  It will not be considered a 
protocol deviation if Pfizer approves the use of the investigational product after the 
temperature excursion. Use of the investigational product prior to Pfizer approval will be 
considered a protocol deviation.  Specific details regarding information the site should report 
for each excursion will be provided to the site.
Receipt of materials, door opening and closing, and other routine handling operations where 
the products are briefly out of the temperature range described in the labeling are not 
considered excursions.
5.6. Investigational Product Accountability
The investigator site must maintain adequate records documenting the receipt, use, loss, or
other disposition of the investigational product supplies. All investigational products will be
accounted for using a drug accountability form/record.
All pivotal BE retained vials may be sent to an off-site location for long-term storage after
study closeout.  Sample retention is the responsibility of the entity performing the BE study.
5.6.1. Destruction of Investigational Product Supplies
The sponsor or designee will provide guidance on the destruction of unused investigational 
product (eg, at the site). If destruction is authorized to take place at the investigator site, the
investigator must ensure that the materials are destroyed in compliance with applicable
environmental regulations, institutional policy, and any special instructions provided by
Pfizer, and all destruction must be adequately documented.
5.7. Concomitant Treatments
Subjects will abstain from all concomitant treatments, except for the treatment of AEs.
Limited use of nonprescription medications that are not believed to affect subject safety or 
the overall results of the study may be permitted on a case-by-case basis following approval 
by the sponsor.
All concomitant treatments taken during the study must be recorded with indication, daily 
dose, and start and stop dates of administration.  All subjects will be questioned about
concomitant treatment at each clinic visit.
Treatments taken within 28 days before the first dose of investigational product will be
documented as a prior treatment.  Treatments taken after the first dose of investigational
product will be documented as concomitant treatments.

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6. STUDY PROCEDURES
6.1. Screening
Refer to Schedule of Activities for the study procedures to be completed at the screening
visit.
Subjects will be screened within 28 days prior to administration of the investigational
product to confirm that they meet the subject selection criteria for the study. The investigator
(or an appropriate delegate at the investigator site) will obtain informed consent from each 
subject in accordance with the procedures described in the Subject Information and Consent
section (Section 12.3).
To prepare for study participation, subjects will be instructed on the Lifestyle Requirements
(Section 4.3) and Concomitant Treatments (Section 5.7) of this protocol.
6.2. Study Period
Refer to Schedule of Activities for the study procedures to be completed. For the study
period described below, when multiple procedures are scheduled at the same time point(s)
relative to dosing, the following chronology of events should be adhered to, where possible.

ECGs: obtain prior to vital sign measurements and as close as possible to the
scheduled time, but prior to blood specimen collection;

BP/pulse rate: obtain as close as possible to the scheduled time, but prior to blood
specimen collection;

PK blood specimens: obtain at the scheduled time;

Other procedures: obtain all other procedures as close as possible to the scheduled
time, but may be obtained before or after blood specimen collection.
When an intravenous (IV) catheter is utilized for blood sample collections, ECGs and vital
sign assessments (pulse rate and BP) should be collected prior to the insertion of the catheter.

There will be an interval of at least 45 days between study periods (ie, administration 
of subsequent doses of investigational product will not occur until at least 45 days 
after the previous dose of investigational product). All study periods will be 
conducted identically to that described above.
If a subject has any clinically significant, study-related abnormalities at the conclusion of a
scheduled inpatient portion of the study, the Pfizer medical monitor (or designated
representative) should be notified and the subject may be asked to remain in the CRU until
such abnormalities are deemed not clinically significant, or it is safe for outpatient follow-up.

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If the subject is unable or unwilling to remain in the CRU and/or when outpatient follow-up
is deemed appropriate, the Pfizer medical monitor (or designated representative) should be so
notified, and the investigator should make every effort to arrange follow-up evaluations at
appropriate intervals to document the course of the abnormalities.
6.3. Follow-up
6.3.1. Follow-up Contact
Follow-up contact will be completed at least 28 calendar days and up to 35 calendar days
after the last administration of the investigational product to capture any potential adverse
events (see the Time Period for Collecting AE/SAE Information section) and to confirm
appropriate contraception usage (see the Contraception section). Contact with the subject
may be done via a phone call.
6.4. Subject Withdrawal
Subjects may withdraw from the study at any time at their own request, or they may be
withdrawn at any time at the discretion of the investigator or sponsor for safety (see also the
Withdrawal From the Study Due to AEs section) or behavioral reasons, or the inability of the
subject to comply with the protocol-required schedule of study visits or procedures at a given
investigator site.  The early termination visit applies only to subjects who are randomized and
then are prematurely withdrawn from the study.
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject. The investigator or site staff should attempt to contact the subject twice. After
2 attempts, CRU staff may send a registered letter. If no response is received from the 
subject, the subject will be considered lost to follow-up. All attempts to contact the subject
and information received during contact attempts must be documented in the subject’s
medical record. In any circumstance, every effort should be made to document subject
outcome, if possible. The investigator should inquire about the reason for withdrawal, request 
that the subject return for a final visit, if applicable, and follow up with the subject regarding 
any unresolved AEs.
Lost to follow-up is defined as:
All reasonable efforts must be made to locate subjects to determine and report their ongoing 
status. This includes follow-up with persons authorized by the subject as noted above. All
attempts should be documented in the subject’s medical records.  If it is determined that the 
subject has died, the site will use locally permissible methods to obtain the date and cause of 
death. If the investigator’s use of a third-party representative to assist in the follow-up
portion of the study has been included in the subject’s informed consent, then the investigator 
may use a sponsor-retained third-party representative to assist site staff with obtaining the
subject’s contact information or other public vital status data necessary to complete the
follow-up portion of the study.  The site staff and representative will consult publicly
available sources, such as public health registries and databases, in order to obtain updated
contact information.  If, after all attempts, the subject remains lost to follow-up, then the
last-known-alive date as determined by the investigator should be reported and documented
in the subject’s medical records.

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It may be appropriate for the subject to return to the clinic for final safety assessments to be
scheduled as early as practically feasible following the decision to withdraw from the study.  
Subjects should be questioned regarding their reason for withdrawal. At the early-withdrawal
visit, every effort must be made to complete the following assessments:

Full physical examination, if there is a new or open AE or clinically significant
abnormal physical finding from the last visit;

Supine BP and pulse rate measurements;

12-Lead ECG measurement;

Blood and urine specimens for safety laboratory;

Blood sample for PK analysis.
Lack of completion of all or any of the withdrawal/early termination procedures will not be
viewed as protocol deviations so long as the subject’s safety was preserved.
If the subject withdraws from the study and also withdraws consent for disclosure of future 
information, no further evaluations should be performed and no additional data should be 
collected.  The sponsor may retain and continue to use any data collected before such
withdrawal of consent.
Withdrawal of consent is defined as:
Subjects who request to discontinue receipt of study treatment will remain in the study and
must continue to be followed for protocol-specified follow-up procedures. The only
exception to this is when a subject specifically withdraws consent for any further contact with 
him or her or persons previously authorized by the subject to provide this information. 
Subjects should notify the investigator in writing of the decision to withdraw consent from
future follow-up, whenever possible.  The withdrawal of consent should be explained in
detail in the medical records by the investigator, as to whether the withdrawal is only from 
further receipt of investigational product or also from study procedures and/or posttreatment
study follow-up, and entered on the appropriate CRF page.  In the event that vital status
(whether the subject is alive or dead) is being measured, publicly available information 
should be used to determine vital status only as appropriately directed in accordance with
local law.
Subjects who withdraw from the study may be replaced at the discretion of the investigator
upon consultation with the sponsor.

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7. ASSESSMENTS
Every effort should be made to ensure that protocol-required tests and procedures are
completed as described.  However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test.  In these cases, the investigator must take all steps necessary to ensure the safety and
well-being of the subject. When a protocol-required test cannot be performed, the
investigator will document the reason for the missed test and any corrective and preventive
actions that he or she has taken to ensure that required processes are adhered to as soon as
possible.  The study team must be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
7.1. Safety
7.1.1. Laboratory Tests
The following safety laboratory tests will be performed at times defined in the Schedule of 
Activities/STUDY PROCEDURES section of this protocol. Additional laboratory results 
may be reported on these samples as a result of the method of analysis or the type of analyzer
used by the clinical laboratory; or as derived from calculated values.  These additional tests
would not require additional collection of blood. Unscheduled clinical laboratory
measurements may be obtained at any time during the study to assess any perceived safety
concerns.

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Table 3.
Safety Laboratory Tests
Hematology
Chemistry
Urinalysis
Other
Hemoglobin
Hematocrit
RBC count
MCV
MCH
MCHC
Platelet count
WBC count
Total neutrophils
(Abs)
Eosinophils (Abs)
Monocytes (Abs)
Basophils (Abs)
Lymphocytes (Abs)
BUN/urea and creatinine
Glucose (fasting)
Calcium
Sodium
Potassium
Chloride
Total CO2 (bicarbonate)
AST, ALT
Total bilirubin
Alkaline phosphatase
Uric acid
Albumin
Total protein
pH
Glucose (qual)
Protein (qual)
Blood (qual)
Ketones
Nitrites
Leukocyte esterase
Urobilinogen
Urine bilirubin
Microscopya
Urine drug screening
HIV
HepBcAb
HepBsAg
HCVAb
PSA
Additional Tests (Needed
for Hy’s Law)
AST, ALT (repeat)
Total bilirubin (repeat)
Albumin (repeat)
Alkaline phosphatase
(repeat)
Direct bilirubin
Indirect bilirubin
Creatine kinase
GGT
PT/INR
Total bile acids
Acetaminophen drug
and/or protein adduct
levels
Abbreviations: abs = absolute; ALT = alanine transaminase; AST = aspartate transaminase;
BUN = blood urea nitrogen; CO2 = carbon dioxide; GGT = gamma-glutamyl transpeptidase;
HepBcAb = hepatitis B core antibody; HepBsAg = hepatitis B surface antigen; HCVAb = hepatitis C antibody;
HIV = human immunodeficiency virus; INR = international normalized ratio; MCH = mean corpuscular
hemoglobin; MCHC = mean corpuscular hemoglobin concentration; MCV = mean corpuscular volume;
PT = prothrombin time; PSA=Prostate Specific Antigen; qual = qualitative; RBC = red blood cell(s);
WBC = white blood cell(s).
a.
Only if urine dipstick is positive for blood, protein, nitrites or leukocyte esterase.

The minimum requirement for drug screening includes cocaine, tetrahydrocannabinol
(THC), opiates/opioids, benzodiazepines, and amphetamines.

Subjects may undergo random urine drug testing at the discretion of the investigator.
Drug testing conducted prior to dosing must be negative for subjects to receive
investigational product.

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7.1.2. Physical Examinations
Physical examinations may be conducted by a physician, trained physician’s assistant, or 
nurse practitioner as acceptable according to local regulation. A full physical examination 
will include head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, 
and gastrointestinal, musculoskeletal, and neurological systems. The limited or abbreviated 
physical examination will be focused on general appearance, the respiratory and 
cardiovascular systems, and subject-reported symptoms.
For measuring weight, a scale with appropriate range and resolution is used and must be 
placed on a stable, flat surface. Subjects must remove shoes, bulky layers of clothing, and 
jackets so that only light clothing remains.  They must also remove the contents of their 
pockets and remain still during measurement of weight.
7.1.3. Blood Pressure (BP) and Pulse Rate
BP and pulse rate will be measured at times specified in the Schedule of Activities/STUDY 
PROCEDURES section of this protocol. Additional collection times, or changes to 
collection times, of BP and pulse rate will be permitted, as necessary, to ensure appropriate 
collection of safety data.
Supine BP will be measured with the subject’s arm supported at the level of the heart, and 
recorded to the nearest mm Hg after approximately 5 minutes of rest.  The same arm 
(preferably the dominant arm) will be used throughout the study.  Subjects should be 
instructed not to speak during measurements.
The same properly sized and calibrated BP cuff will be used to measure BP each time. The 
use of an automated device for measuring BP and pulse rate is acceptable; however, when 
done manually, pulse rate will be measured in the brachial/radial artery for at least
30 seconds.  When the timing of these measurements coincides with a blood collection, BP
and pulse rate should be obtained prior to the nominal time of the blood collection.
7.1.4. Electrocardiogram (ECG)
12-Lead ECGs should be collected at times specified in the Schedule of Activities/STUDY 
PROCEDURES section of this protocol.
All scheduled ECGs should be performed after the subject has rested quietly for at least 
10 minutes in a supine position.
To ensure safety of the subjects, a qualified individual at the investigator site will make 
comparisons to baseline measurements from the current period.  If the QTc interval is 
increased by ≥45 msec from the baseline, or an absolute QTc value is ≥500 msec for any 
scheduled ECG, then 2 additional ECGs will be collected, approximately 2 to 4 minutes 
apart, to confirm the original measurement.  If either of the QTc values from these repeated 
ECGs remains above the threshold value (ie, is ≥45 msec from the baseline, or is
≥500 msec), then a single ECG must be repeated at least hourly until QTc values from
2 successive ECGs fall below the threshold value that triggered the repeat measurement.

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If QTc values remain ≥500 msec (or ≥45 msec from the baseline) for greater than 4 hours (or
sooner, at the discretion of the investigator), or QTc intervals get progressively longer, the
subject should undergo continuous ECG monitoring. A cardiologist should be consulted if
QTc intervals do not return to less than 500 msec (or to <45 msec above the baseline) after
8 hours of monitoring (or sooner, at the discretion of the investigator).
In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead
placement as contributing to the ECG abnormality. It is important that leads are placed in the 
same positions each time in order to achieve precise ECG recordings.  If a machine-read QTc
value is prolonged, as defined above, repeat measurements may not be necessary if a
qualified medical provider’s interpretation determines that the QTc values are in the
acceptable range.
7.2. Pharmacokinetics (PK)
7.2.1. Serum for Analysis of Testosterone and Dihydrotestosterone
During all study periods, blood samples (6 mL) to provide approximately 2.5 mL serum for
PK analysis will be collected into appropriately labeled tubes at times specified in the
Schedule of Activities section of the protocol.
The actual times may change, but the number of samples will remain the same.  All efforts
will be made to obtain the PK samples at the exact nominal time relative to dosing.  
However, samples obtained within 10% of the nominal time (eg, within 6 minutes of a
60-minute sample) from dosing will not be captured as a protocol deviation, as long as the
exact time of the sample collection is noted on the source document and data collection tool 
(eg, CRF). It is important to note, that for baseline testosterone samples (4 pre-dose) it is 
recommended to obtain samples from 7-8 am, if dosing occurs for example at 8 am 
(recommended). A window of no more than 2 hours is allowed (ie, 6-8 am).
Samples will be analyzed using a validated analytical method in compliance with Pfizer
standard operating procedures (SOPs).
The PK samples must be processed and shipped as indicated in the instructions provided to
the investigator site to maintain sample integrity. Any deviations from the PK sample
handling procedure (eg, sample collection and processing steps, interim storage or shipping
conditions), including any actions taken, must be documented and reported to the sponsor. 
On a case-by-case basis, the sponsor may make a determination as to whether sample
integrity has been compromised. Any deviation from the specified sample handling
procedure resulting in compromised sample integrity will be considered a protocol deviation.
As part of understanding the PK of the investigational product, samples may be used for
metabolite identification and/or evaluation of the bioanalytical method, as well as for other
internal exploratory purposes.  These data will not be included in the clinical study report 
(CSR).

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7.3. Blood Volume
The total blood sampling volume for individual subjects in Part 1 of this study is 
approximately 204 mL.  The total blood sampling volume for individual subjects in Part 1 of 
this study is approximately 306 mL. The actual collection times of blood sampling may
change.  Additional blood samples may be taken for safety assessments at times specified by
Pfizer, provided the total volume taken during the study does not exceed 550 mL during any
period of 60 consecutive days.
8. ADVERSE EVENT REPORTING
8.1. Requirements
The table below summarizes the requirements for recording safety events on the CRF and for 
reporting safety events on the Clinical Trial (CT) Serious Adverse Event (SAE) Report Form 
to Pfizer Safety.  These requirements are delineated for 3 types of events: (1) SAEs;
(2) non-serious AEs; and (3) exposure to the investigational product under study during 
pregnancy or breastfeeding, and occupational exposure.
Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness
SAE
All
All
Non-serious AE
All
None
Exposure to the 
investigational product under 
study during pregnancy or 
breastfeeding, and 
occupational exposure
All (regardless of whether 
associated with an AE), 
except occupational 
exposure
Exposure during pregnancy, 
exposure via breastfeeding, 
occupational exposure 
(regardless of whether 
associated with an AE)
All observed or volunteered events regardless of treatment group or suspected causal 
relationship to the investigational product(s) will be reported as described in the following 
paragraphs.
Events listed in the table above that require reporting to Pfizer Safety on the CT SAE Report
Form within 24 hours of awareness of the event by the investigator are to be reported
regardless of whether the event is determined by the investigator to be related to an 
investigational product under study.  In particular, if the SAE is fatal or life-threatening,
notification to Pfizer Safety must be made immediately, irrespective of the extent of available
event information. This time frame also applies to additional new (follow-up) information on
previously forwarded reports.  In the rare situation that the investigator does not become

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immediately aware of the occurrence of an event, the investigator must report the event 
within 24 hours after learning of it and document the time of his/her first awareness of the
event.
For each event, the investigator must pursue and obtain adequate information both to
determine the outcome and to assess whether it meets the criteria for classification as an SAE 
(see the Serious Adverse Events section below). In addition, the investigator may be
requested by Pfizer Safety to obtain specific follow-up information in an expedited fashion.
This information is more detailed than that recorded on the CRF. In general, this will include
a description of the event in sufficient detail to allow for a complete medical assessment of
the case and independent determination of possible causality. Any information relevant to the 
event, such as concomitant medications and illnesses, must be provided.  In the case of a
subject death, a summary of available autopsy findings must be submitted as soon as possible 
to Pfizer Safety. Any pertinent additional information must be reported on the CT SAE
Report Form; additional source documents (eg, medical records, CRF, laboratory data) are to
be sent to Pfizer Safety ONLY upon request.
As part of ongoing safety reviews conducted by the sponsor, any non-serious AE that is
determined by the sponsor to be serious will be reported by the sponsor as an SAE. To assist
in the determination of case seriousness, further information may be requested from the
investigator to provide clarity and understanding of the event in the context of the clinical 
study.
8.1.1. Additional Details on Recording Adverse Events on the CRF
All events detailed in the table above will be recorded on the AE page(s) of the CRF.  It
should be noted that the CT SAE Report Form for reporting of SAE information is not the 
same as the AE page of the CRF.  When the same data are collected, the forms must be 
completed in a consistent manner.  AEs should be recorded using concise medical
terminology and the same AE term should be used on both the CRF and the CT SAE Report 
Form for reporting of SAE information.
8.1.2. Eliciting Adverse Event Information
The investigator is to record on the CRF all directly observed AEs and all AEs spontaneously 
reported by the study subject or legally acceptable representative. In addition, each study 
subject or legally acceptable representative will be questioned about the occurrence of AEs 
in a non-leading manner.
8.1.3. Withdrawal From the Study Due to Adverse Events (see also the Subject 
Withdrawal Section)
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted below, and recorded on the CRF.
When a subject withdraws from the study because of an SAE, the SAE must be recorded on
the CRF and reported, as appropriate, on the CT SAE Report Form, in accordance with the 
Requirements section above.

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8.1.4. Time Period for Collecting AE/SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection
period”) for each subject begins from the time the subject provides informed consent, which 
is obtained before the subject’s participation in the study (ie, before undergoing any
study-related procedure and/or receiving investigational product), through and including a
minimum of 28 calendar days after the last administration of the investigational product.
For subjects who are screen failures, the active collection period ends when screen failure
status is determined.
8.1.4.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a subject during the active collection period are reported to Pfizer 
Safety on the CT SAE Report Form.
SAEs occurring in a subject after the active collection period has ended are reported to Pfizer 
Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product must be reported to Pfizer Safety.
Follow up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and 
Pfizer concurs with that assessment.
8.1.4.2. Recording Non-serious AEs and SAEs on the CRF
During the active collection period, both non-serious AEs and SAEs are recorded on the 
CRF.
Follow-up by the investigator may be required until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment.
8.1.5. Causality Assessment
The investigator’s assessment of causality must be provided for all AEs (serious and
non-serious); the investigator must record the causal relationship on the CRF, and report such
an assessment in accordance with the SAE reporting requirements, if applicable. An
investigator’s causality assessment is the determination of whether there exists a reasonable
possibility that the investigational product caused or contributed to an AE; generally the facts
(evidence) or arguments to suggest a causal relationship should be provided.  If the 
investigator does not know whether or not the investigational product caused the event, then
the event will be handled as “related to investigational product” for reporting purposes, as
defined by the sponsor. If the investigator's causality assessment is “unknown but not
related” to investigational product, this should be clearly documented on study records.

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In addition, if the investigator determines that an SAE is associated with study procedures, 
the investigator must record this causal relationship in the source documents and CRF, and 
report such an assessment in the dedicated section of the CT SAE Report Form and in 
accordance with the SAE reporting requirements.
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities
AE reporting, including suspected unexpected serious adverse reactions, will be carried out 
in accordance with applicable local regulations.
8.2. Definitions
8.2.1. Adverse Events
An AE is any untoward medical occurrence in a study subject administered a product or
medical device; the event need not necessarily have a causal relationship with the treatment
or usage.  Examples of AEs include, but are not limited to:

Abnormal test findings;

Clinically significant signs and symptoms;

Changes in physical examination findings;

Hypersensitivity;

Progression/worsening of underlying disease;

Drug abuse;

Drug dependency.
Additionally, AEs may include signs and symptoms resulting from:

Drug overdose;

Drug withdrawal;

Drug misuse;

Drug interactions;

Extravasation;

Exposure during pregnancy (EDP);

Exposure via breastfeeding;

Medication error;

Occupational exposure.

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8.2.2. Abnormal Test Findings
Abnormal objective test findings should be recorded as AEs when any of the following
conditions are met:

Test result is associated with accompanying symptoms; and/or

Test result requires additional diagnostic testing or medical/surgical intervention;
and/or

Test result leads to a change in study dosing (outside of any protocol-specified dose
adjustments) or discontinuation from the study, significant additional concomitant
drug treatment, or other therapy; and/or

Test result is considered to be an AE by the investigator or sponsor.
Merely repeating an abnormal test, in the absence of any of the above conditions, does not
constitute an AE. Any abnormal test result that is determined to be an error does not require
recording as an AE.
8.2.3. Serious Adverse Events
An SAE is any untoward medical occurrence at any dose that:

Results in death;

Is life-threatening (immediate risk of death);

Requires inpatient hospitalization or prolongation of existing hospitalization;

Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions);

Results in congenital anomaly/birth defect. 
Or that is considered to be:

An important medical event.
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life-threatening and/or
result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the subject or may require intervention to prevent one of the other AE outcomes, the 
important medical event should be reported as serious.
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization;
or development of drug dependency or drug abuse.

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8.2.4. Hospitalization
Hospitalization is defined as any initial admission (even less than 24 hours) in a hospital or
equivalent healthcare facility, or any prolongation of an existing admission.  Admission also
includes transfer within the hospital to an acute/intensive care unit (eg, from the psychiatric
wing to a medical floor, medical floor to a coronary care unit, or neurological floor to a 
tuberculosis unit). An emergency room visit does not necessarily constitute a hospitalization;
however, the event leading to the emergency room visit is assessed for medical importance.
Hospitalization does not include the following:

Rehabilitation facilities;

Hospice facilities;

Respite care (eg, caregiver relief);

Skilled nursing facilities;

Nursing homes;

Same-day surgeries (as outpatient/same-day/ambulatory procedures).
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 not associated with the 
development of a new AE or with a worsening of the preexisting condition (eg, for
workup of a persistent pretreatment laboratory abnormality);

Social admission (eg, subject has no place to sleep);

Administrative admission (eg, for yearly physical examination);

Protocol-specified admission during a study (eg, for a procedure required by the study
protocol);

Optional admission not associated with a precipitating clinical AE (eg, for elective 
cosmetic surgery);

Hospitalization for observation without a medical AE;

Preplanned treatments or surgical procedures.  These should be noted in the baseline
documentation for the entire protocol and/or for the individual subject.

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Diagnostic and therapeutic noninvasive and invasive procedures, such as surgery, should not
be reported as SAEs.  However, the medical condition for which the procedure was
performed should be reported if it meets the definition of an SAE. For example, an acute 
appendicitis that begins during the reporting period should be reported if the SAE 
requirements are met, and the resulting appendectomy should be recorded as treatment of the
AE.
8.3. Severity Assessment
If required on the AE page of the CRF, the investigator will use the adjectives MILD, 
MODERATE, or SEVERE to describe the maximum intensity of the AE.  For purposes of 
consistency, these intensity grades are defined as follows:
MILD
Does not interfere with subject's usual function.
MODERATE
Interferes to some extent with subject's usual function.
SEVERE
Interferes significantly with subject's usual function.
Note the distinction between the severity and the seriousness of an AE. A severe event is not 
necessarily an SAE.  For example, a headache may be severe (interferes significantly with
the subject's usual function) but would not be classified as serious unless it met one of the 
criteria for SAEs, listed above.
8.4. Special Situations
8.4.1. Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt
are termed “adaptors.” In some subjects, transaminase elevations are a harbinger of a more
serious potential outcome. These subjects fail to adapt and therefore are “susceptible” to
progressive and serious liver injury, commonly referred to as drug-induced liver injury
(DILI). Subjects who experience a transaminase elevation above 3 times the upper limit of
normal (× ULN) should be monitored more frequently to determine if they are an “adaptor”
or are “susceptible.”
In the majority of DILI cases, elevations in AST and/or ALT precede total bilirubin (TBili) 
elevations (>2 × ULN) by several days or weeks.  The increase in TBili typically occurs
while AST/ALT is/are still elevated above 3 × ULN (ie, AST/ALT and TBili values will be
elevated within the same lab sample). In rare instances, by the time TBili elevations are
detected, AST/ALT values might have decreased. This occurrence is still regarded as a
potential DILI.  Therefore, abnormal elevations in either AST OR ALT in addition to TBili
that meet the criteria outlined below are considered potential DILI (assessed per Hy’s law
criteria) cases and should always be considered important medical events, even before all
other possible causes of liver injury have been excluded.

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The threshold of laboratory abnormalities for a potential DILI case depends on the subject’s 
individual baseline values and underlying conditions. Subjects who present with the
following laboratory abnormalities should be evaluated further as potential DILI (Hy’s law)
cases to definitively determine the etiology of the abnormal laboratory values:

Subjects with AST/ALT and TBili baseline values within the normal range who
subsequently present with AST OR ALT values >3 × ULN AND a TBili value
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value
<2 × ULN or not available.

For subjects with baseline AST OR ALT OR TBili values above the ULN, the
following threshold values are used in the definition mentioned above, as needed,
depending on which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is
smaller).

Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches >3 × ULN 
(whichever is smaller).
Rises in AST/ALT and TBili separated by more than a few weeks should be assessed
individually based on clinical judgment; any case where uncertainty remains as to whether it
represents a potential Hy’s law case should be reviewed with the sponsor.
The subject should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should
include laboratory tests, detailed history, and physical assessment.
In addition to repeating measurements of AST and ALT and TBili, laboratory tests should
include albumin, creatine kinase (CK), direct and indirect bilirubin, gamma-glutamyl
transferase (GGT), prothrombin time (PT)/international normalized ratio (INR), total bile 
acids, alkaline phosphatase and acetaminophen drug and/or protein adduct levels.
Consideration should also be given to drawing a separate tube of clotted blood and an
anticoagulated tube of blood for further testing, as needed, for further contemporaneous 
analyses at the time of the recognized initial abnormalities to determine etiology.  A detailed
history, including relevant information, such as review of ethanol, acetaminophen (either by
itself or as a coformulated product in prescription or over-the-counter medications),
recreational drug, supplement (herbal) use and consumption, family history, sexual history,
travel history, history of contact with a jaundiced person, surgery, blood transfusion, history
of liver or allergic disease, and potential occupational exposure to chemicals, should be
collected. Further testing for acute hepatitis A, B, C, D, and E infection and liver imaging
(eg, biliary tract) may be warranted.

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All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the liver function test (LFT) abnormalities has yet been found. Such
potential DILI (Hy’s law) cases are to be reported as SAEs, irrespective of availability 
of all the results of the investigations performed to determine etiology of the LFT 
abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of
reasonable investigations have been received and have excluded an alternative etiology.
8.4.2. Exposure to the Investigational Product During Pregnancy or Breastfeeding, and
Occupational Exposure
Exposure to the investigational product under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator
awareness.
8.4.2.1. Exposure During Pregnancy
For both unapproved/unlicensed products and for marketed products, an exposure during
pregnancy (EDP) occurs if:

A female becomes, or is found to be, pregnant either while receiving or having been 
exposed (eg, because of treatment or environmental exposure) to the investigational
product; or the female becomes or is found to be pregnant after discontinuing and/or 
being exposed to the investigational product;

An example of environmental exposure would be a case involving direct contact with 
a Pfizer product in a pregnant woman (eg, a nurse reports that she is pregnant and has
been exposed to chemotherapeutic products);

A male has been exposed (eg, because of treatment or environmental exposure) to the
investigational product prior to or around the time of conception and/or is exposed
during his partner’s pregnancy.
If a subject or subject’s partner becomes or is found to be pregnant during the subject’s
treatment with the investigational product, the investigator must report this information to 
Pfizer Safety on the CT SAE Report Form and an EDP supplemental form, regardless of 
whether an SAE has occurred. In addition, the investigator must submit information
regarding environmental exposure to a Pfizer product in a pregnant woman (eg, a subject 
reports that she is pregnant and has been exposed to a cytotoxic product by inhalation or
spillage) to Pfizer Safety using the EDP supplemental form. This must be done irrespective
of whether an AE has occurred and within 24 hours of awareness of the exposure. The
information submitted should include the anticipated date of delivery (see below for 
information related to termination of pregnancy).

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Follow-up is conducted to obtain general information on the pregnancy and its outcome for
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a
follow-up to the initial EDP supplemental form.  In the case of a live birth, the structural
integrity of the neonate can be assessed at the time of birth. In the event of a termination, the
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless
pre-procedure test findings are conclusive for a congenital anomaly and the findings are
reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy,
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the
investigator should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported to Pfizer Safety as SAEs
follows:

Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard
to causality, as SAEs.  In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to
exposure to the investigational product.
Additional information regarding the EDP may be requested by the sponsor.  Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays).  In the case of paternal exposure, the
investigator will provide the subject with the Pregnant Partner Release of Information Form 
to deliver to his partner. The investigator must document in the source documents that the 
subject was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.4.2.2. Exposure During Breastfeeding
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of
an associated SAE, to Pfizer Safety within 24 hours of the investigator’s awareness, using the
CT SAE Report Form.  An exposure during breastfeeding report is not created when a Pfizer 
drug specifically approved for use in breastfeeding women (eg, vitamins) is administered in
accord with authorized use. However, if the infant experiences an SAE associated with such 
a drug’s administration, the SAE is reported together with the exposure during breastfeeding.
8.4.2.3. Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an AE.

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An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the CT SAE Report Form, regardless of whether there is an associated SAE.  
Since the information does not pertain to a subject enrolled in the study, the information is 
not recorded on a CRF; however, a copy of the completed CT SAE Report Form is 
maintained in the investigator site file.
8.4.3. Medication Errors
Other exposures to the investigational product under study may occur in clinical trial settings,
such as medication errors.
Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness
Medication errors
All (regardless of whether 
associated with an AE)
Only if associated with an 
SAE
8.4.3.1. Medication Errors
Medication errors may result from the administration or consumption of the investigational
product by the wrong subject, or at the wrong time, or at the wrong dosage strength.
Medication errors include:

Medication errors involving subject exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the participating subject.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified immediately.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and non-serious, are recorded on an AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report
Form only when associated with an SAE.

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9. DATA ANALYSIS/STATISTICAL METHODS
Detailed methodology for summary and statistical analyses of the data collected in this study
is outlined here and further detailed in a statistical analysis plan (SAP), which will be
maintained by the sponsor.  The SAP may modify what is outlined in the protocol where
appropriate; however, any major modifications of the primary endpoint definitions or their
analyses will also be reflected in a protocol amendment.
 
 
 
 
 
 
 
 
 
 
9.2. Efficacy Analysis
Efficacy analysis is not applicable to this study.
9.3. Pharmacokinetic Analysis
9.3.1. Derivation of Pharmacokinetic Parameters Prior to Analysis
PK parameters will be derived from the concentration-time profiles as shown in Table 4.
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Table 4.
Derivation of Pharmacokinetic Parameters
Parameter
Definition
Method of Determination
AUClast
Area under the plasma 
concentration-time profile from time 
zero to the time of the last quantifiable 
concentration (Clast)
Linear trapezoidal method
AUCinf
Area under the plasma 
concentration-time profile from time 
zero extrapolated to infinite time
AUClast + (Clast*/kel),
where Clast* is the predicted plasma 
concentration at the last quantifiable time 
point estimated from the log-linear 
regression analysis
Cmax
Maximum plasma concentration
Observed directly from data
 
t½
Terminal elimination half-life
Loge(2)/kel,
where kel is the terminal phase rate constant 
calculated by a linear regression of the 
log-linear concentration-time curve.  Only 
those data points judged to describe the 
terminal log-linear decline will be used in the 
regression
*
If data permit. 
9.3.2. Analysis Populations
The PK concentration population is defined as all subjects randomized and treated who have 
at least 1 concentration in at least 1 treatment period.
The PK parameter analysis population is defined as all subjects randomized and treated who
have at least 1 of the PK parameters of primary interest in at least 1 treatment period.
9.3.3. Statistical Analyses of Pharmacokinetic Parameters
For each Part separately, natural log transformed AUClast, AUCinf (if data permit) and Cmax of
total testosterone (baseline corrected [mean of the 4 predose measurements] and uncorrected)
will be analyzed separately using a mixed effect model with sequence, period and treatment
as fixed effects and subject within sequence as a random effect.  Estimates of the adjusted
mean differences (Test – Reference) and corresponding 90% confidence intervals will be
obtained from the model.  The adjusted mean differences and 90% confidence intervals for
the differences will be exponentiated to provide estimates of the ratio of adjusted geometric
means (Test/Reference) and 90% confidence intervals for the ratios.
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Bioequivalence of the 2 treatments will be assessed in Part 2 and concluded if the 90%
confidence intervals for the ratio of adjusted geometric means for AUCinf, AUClast, and Cmax
fall wholly within (80%, 125%). However, the bounds of the acceptance interval may be 
widened based on scaled bioequivalence methodology, which will be detailed in the 
Statistical Analysis Plan.
For each Part separately, the PK parameters for total testosterone (baseline corrected and
uncorrected) of AUCinf, AUClast, percent of AUCinf (if data permit) obtained by forward
 Cmax, 
 
 and terminal elimination half-life (t½)
(if data permit) will be summarized descriptively by analyte and treatment.  The PK
parameters for DHT of Cmax, 
AUCinf, AUClast, (if data permits), and t½ (if data permits)
will also be summarized descriptively by analyte and treatment. For AUCinf, AUClast and
Cmax, individual subject parameters will be plotted by analyte and treatment. Concentrations
will be listed by analyte and summarized descriptively by PK sampling time and treatment.
Individual subject, mean and median profiles of the concentration-time data will be plotted
by analyte against treatment (both linear and semi-log scales). For summary statistics and
summary (mean and median) plots by sampling time, the nominal PK sampling time will be
used.  For individual subject plots by time, the actual PK sampling time will be used.
 
 
 
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9.5. Interim Analysis
No formal interim analysis will be conducted for this study.  However, as this is an 
open-label study, the sponsor may conduct unblinded reviews of the data during the course of 
the study for the purpose of safety assessment, facilitating dose-escalation decisions,
facilitating PK/pharmacodynamic (PD) modeling, and/or supporting clinical development.
 
 
 
 
Based on the results from Part 1, when the bioequivalence estimation was performed without 
the baseline correction, test formulation (Treatment A) was found to be bioequivalent to 
reference formulation (Treatment B) for AUCinf, AUClast and Cmax.  For all PK parameters the 
90% CI for the ratio of the adjusted geometric mean fell within the 80-125% limits.  
However, when the data was analyzed with baseline testosterone correction, the 90% CI for 
the ratio for all the PK parameters was outside the 80%-125% limit. Importantly, the 
variability associated with AUCinf was approximately 40%. The higher variability observed 
in these results as compared to the previous B5341001 study is the reason for the change in
the original design of Part 2 from a 2-period crossover to a partial replicate design involving 
3 periods.  
Data Monitoring Committee
This study will not use a data monitoring committee (DMC).
10. QUALITY CONTROL AND QUALITY ASSURANCE
Pfizer or its agent will conduct periodic monitoring visits during study conduct for studies
conducted at non-Pfizer investigator sites, to ensure that the protocol and Good Clinical
Practices (GCPs) are being followed.  The monitors may review source documents to
confirm that the data recorded on CRFs are accurate. The investigator and institution will
allow Pfizer monitors/auditors or its agents and appropriate regulatory authorities direct 
access to source documents to perform this verification. This verification may also occur
after study completion.
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During study conduct and/or after study completion, the investigator site may be subject to
review by the institutional review board (IRB)/ethics committee (EC), and/or to quality
assurance audits performed by Pfizer, or companies working with or on behalf of Pfizer,
and/or to inspection by appropriate regulatory authorities.
The investigator will notify Pfizer or its agents immediately of any regulatory inspection
notification in relation to the study. Furthermore, the investigator will cooperate with Pfizer
or its agents to prepare the investigator site for the inspection and will allow Pfizer or its 
agent, whenever feasible, to be present during the inspection. The investigator site and 
investigator will promptly resolve any discrepancies that are identified between the study
data and the subject’s medical records. The investigator will promptly provide copies of the
inspection findings to Pfizer or its agent. Before response submission to the regulatory
authorities, the investigator will provide Pfizer or its agents with an opportunity to review
and comment on responses to any such findings.
For studies conducted at non-Pfizer investigator sites, it is important that the investigator(s)
and their relevant personnel are available during the monitoring visits and possible audits or
inspections and that sufficient time is devoted to the process.
11. DATA HANDLING AND RECORD KEEPING
11.1. Case Report Forms/Electronic Data Record
As used in this protocol, the term CRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method used in this study.
A CRF is required and should be completed for each included subject. The completed 
original CRFs are the sole property of Pfizer and should not be made available in any form to
third parties, except for authorized representatives of Pfizer or appropriate regulatory 
authorities, without written permission from Pfizer. The investigator shall ensure that the 
CRFs are securely stored in encrypted electronic and/or paper form and will be password
protected or secured in a locked room to prevent access by unauthorized third parties.
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety, and laboratory data entered on the CRFs and any other data collection forms (source
documents) and ensuring that they are accurate, authentic/original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring, and available when required. The
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs are true. Any corrections to entries made in the CRFs or source
documents must be dated, initialed, and explained (if necessary) and should not obscure the
original entry.
In most cases the source documents are the hospital or the physician's chart. In these cases,
data collected on the CRFs must match those charts.
In some cases, the CRF may also serve as the source document. In these cases, a document
should be available at the investigator site and at Pfizer that clearly identifies those data that
will be recorded on the CRF, and for which the CRF will stand as the source document.

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11.2. Record Retention
To enable evaluations and/or inspections/audits from regulatory authorities or Pfizer, the
investigator agrees to keep records, including the identity of all participating subjects
(sufficient information to link records, eg, CRFs and hospital records), all original signed
informed consent documents, copies of all CRFs, safety reporting forms, source documents,
detailed records of treatment disposition, and adequate documentation of relevant 
correspondence (eg, letters, meeting minutes, and telephone call reports). The records should
be retained by the investigator according to the ICH guidelines, according to local
regulations, or as specified in the clinical study agreement (CSA), whichever is longer. The
investigator must ensure that the records continue to be stored securely for so long as they are
retained.
If the investigator becomes unable for any reason to continue to retain study records for the
required period (eg, retirement, relocation), Pfizer should be prospectively notified. The
study records must be transferred to a designee acceptable to Pfizer, such as another
investigator, another institution, or to an independent third party arranged by Pfizer.
Investigator records must be kept for a minimum of 15 years after completion or
discontinuation of the study or for longer if required by applicable local regulations.
The investigator must obtain Pfizer's written permission before disposing of any records,
even if retention requirements have been met.
12. ETHICS
12.1. Institutional Review Board/Ethics Committee
It is the responsibility of the investigator to have prospective approval of the study protocol,
protocol amendments, informed consent documents, and other relevant documents, eg,
recruitment advertisements, if applicable, from the IRB/EC.  All correspondence with the
IRB/EC should be retained in the investigator file. Copies of IRB/EC approvals should be
forwarded to Pfizer.
The only circumstance in which an amendment may be initiated prior to IRB/EC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects. In
that event, the investigator must notify the IRB/EC and Pfizer in writing immediately after 
the implementation.
12.2. Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, legal and regulatory
requirements, and the general principles set forth in the International Ethical Guidelines for
Biomedical Research Involving Human Subjects (Council for International Organizations of 
Medical Sciences 2002), ICH Guideline for Good Clinical Practice, and the Declaration of
Helsinki.

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12.3. Subject Information and Consent
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of subject personal data. Such
measures will include omitting subject names or other directly identifiable data in any
reports, publications, or other disclosures, except where required by applicable laws.
The personal data will be stored at the study site in encrypted electronic and/or paper form
and will be password protected or secured in a locked to ensure that only authorized study
staffs have access.  The study site will implement appropriate technical and organizational
measures to ensure that the personal data can be recovered in the event of disaster. In the 
event of a potential personal data breach, the study site shall be responsible for determining
whether a personal data breach has in fact occurred and, if so, providing breach notifications 
as required by law.
To protect the rights and freedoms of natural persons with regard to the processing of
personal data, when study data are compiled for transfer to Pfizer and other authorized
parties, subject names will be removed and will be replaced by a single, specific, numerical
code, based on a numbering system defined by Pfizer. All other identifiable data transferred
to Pfizer or other authorized parties will be identified by this single, subject-specific code.  
The investigator site will maintain a confidential list of subjects who participated in the
study, linking each subject’s numerical code to his or her actual identity. In case of data
transfer, Pfizer will maintain high standards of confidentiality and protection of subjects’ 
personal data consistent with the Clinical Study Agreement and applicable privacy laws.
The informed consent documents and any subject recruitment materials must be in
compliance with ICH GCP, local regulatory requirements, and legal requirements, including
applicable privacy laws.
The informed consent documents used during the informed consent process and any subject
recruitment materials must be reviewed and approved by Pfizer, approved by the IRB/EC
before use, and available for inspection.
The investigator must ensure that each study subject is fully informed about the nature and
objectives of the study, the sharing of data relating to the study and possible risks associated
with participation, including the risks associated with the processing of the subject’s personal
data.  The investigator further must ensure that each study subject, or his or her legally 
acceptable representative, or parent(s) or legal guardian if a minor, is fully informed about
his or her right to access and correct his or her personal data and to withdraw consent for the 
processing of his or her personal data.
The investigator, or a person designated by the investigator, will obtain written informed
consent from each subject or the subject's legally acceptable representative, parent(s), or legal
guardian and the subject’s assent, when applicable, before any study-specific activity is
performed, unless a waiver of informed consent has been granted by an IRB/EC. The
investigator will retain the original of each subject's signed consent/assent document.

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12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable
regulatory authority in any area of the world, or if the investigator is aware of any new
information that might influence the evaluation of the benefits and risks of the investigational
product, Pfizer should be informed immediately.
In addition, the investigator will inform Pfizer immediately of any urgent safety measures
taken by the investigator to protect the study subjects against any immediate hazard, and of
any serious breaches of this protocol or of ICH GCP that the investigator becomes aware of.
13. DEFINITION OF END OF TRIAL
13.1. End of Trial in the United States
Last subject last visit (LSLV) is defined as the date the investigator reviews the last subject’s
final safety data and determines that no further evaluation is required for the subject to
complete the trial.
14. SPONSOR DISCONTINUATION CRITERIA
Premature termination of this study may occur because of a regulatory authority decision,
change in opinion of the IRB/EC, or investigational product safety problems, or at the
discretion of Pfizer.  In addition, Pfizer retains the right to discontinue development of 
testosterone cypionate solution for injection at any time.
If a study is prematurely terminated, Pfizer will promptly notify the investigator. After
notification, the investigator must contact all participating subjects and the hospital pharmacy 
(if applicable) within 7 days. As directed by Pfizer, all study materials must be collected and
all CRFs completed to the greatest extent possible.
15. PUBLICATION OF STUDY RESULTS
15.1. Communication of Results by Pfizer
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials
Database (EudraCT), and/or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and
complete manner and are reported regardless of the outcome of the study or the country in
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a
Pfizer product, regardless of the geographical location in which the study is conducted. US 
Basic Results are submitted for posting within 1 year of the primary completion date (PCD) 
for studies in adult populations or within 6 months of the PCD for studies in pediatric 
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PCD is defined as the date that the final subject was examined or received an intervention for 
the purposes of final collection of data for the primary outcome, whether the clinical study 
concluded according to the prespecified protocol or was terminated.
EudraCT
Pfizer posts European Union (EU) Basic Results on EudraCT for all Pfizer-sponsored
interventional studies that are in scope of EU requirements.  EU Basic Results are submitted
for posting within 1 year of the PCD for studies in adult populations or within 6 months of
the PCD for studies in pediatric populations.
www.pfizer.com
Pfizer posts public disclosure synopses (CSR synopses in which any data that could be used
to identify individual patients have been removed) on www.pfizer.com for Pfizer-sponsored
interventional studies at the same time the US Basic Results document is posted to 
www.clinicaltrials.gov.
15.2. Publication by Investigators
Pfizer supports the exercise of academic freedom and has no objection to publication by the
principal investigator (PI) of the results of the study based on information collected or 
generated by the PI, whether or not the results are favorable to the Pfizer product. However,
to ensure against inadvertent disclosure of confidential information or unprotected 
inventions, the investigator will provide Pfizer an opportunity to review any proposed 
publication or other type of disclosure of the results of the study (collectively, “publication”)
before it is submitted or otherwise disclosed.
The investigator will provide any publication to Pfizer at least 30 days before it is submitted
for publication or otherwise disclosed. If any patent action is required to protect intellectual
property rights, the investigator agrees to delay the disclosure for a period not to exceed an
additional 60 days.
The investigator will, on request, remove any previously undisclosed confidential information 
before disclosure, except for any study- or Pfizer product-related information necessary to 
the appropriate scientific presentation or understanding of the study results.
If the study is part of a multicenter study, the investigator agrees that the first publication is
to be a joint publication covering all investigator sites, and that any subsequent publications
by the PI will reference that primary publication.  However, if a joint manuscript has not 
been submitted for publication within 12 months of completion or termination of the study at
all participating sites, the investigator is free to publish separately, subject to the other
requirements of this section.

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For all publications relating to the study, the institution will comply with recognized ethical
standards concerning publications and authorship, including Section II - “Ethical
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements for 
Manuscripts Submitted to Biomedical Journals, http://www.icmje.org/index.html#authorship,
established by the International Committee of Medical Journal Editors.
Publication of study results is also provided for in the CSA between Pfizer and the 
institution.  In this section entitled Publication by Investigators, the defined terms shall have
the meanings given to them in the CSA.
If there is any conflict between the CSA and any attachments to it, the terms of the CSA
control. If there is any conflict between this protocol and the CSA, this protocol will control
as to any issue regarding treatment of study subjects, and the CSA will control as to all other
issues.

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16. REFERENCES
1.
Depo-Testosterone (testosterone cypionate injection, USP) U.S. Prescribing
Information. Pfizer, Inc. 2017.

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Appendix 1. Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
Abs
absolute
AE(s)
adverse event(s)
ALT
alanine aminotransferase
API
active pharmaceutical ingredient
AST
aspartate aminotransferase
AUC
area under the curve
AUCinf
area under the plasma concentration-time profile from time 
0 extrapolated to infinite time
AUClast
area under the plasma concentration-time profile from time 0 to the 
time of the last quantifiable concentration (Clast)
BE
bioequivalence
BMI
body mass index
BP
blood pressure
BUN
blood urea nitrogen
CI
confidence interval
CK
creatine kinase
Clast
the last quantifiable concentration
Cmax
maximum plasma concentration
CO2
carbon dioxide (bicarbonate)
CRF
case report form
CRU
clinical research unit
CSA
clinical study agreement
CSR
clinical study report
CT
Clinical Trial
DCT
data collection tool
DEPO-Testosterone
Intramuscular depot formulation of testosterone cypionate
DHT
dihydrotestosterone
DILI
drug-induced liver injury
DMC
data monitoring committee
EC
ethics committee
ECG
electrocardiogram
EDP
exposure during pregnancy
EU
European Union
EudraCT
European Clinical Trials Database
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
HCVAb
hepatitis C antibody
HepBcAb
hepatitis B core antibody
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Abbreviation
Term
HepBsAg
hepatitis B surface antigen
HIV
human immunodeficiency virus
ICH
International Conference on Harmonisation
IM
intramusclar
IND
investigational new drug application
INR
international normalized ratio
IP manual
investigational product manual
IRB
institutional review board
IUD
intrauterine device
IV
intravenous
LFT
liver function test
LH
luteinizing hormone
LHRH
Luteinizing Hormone Releasing Hormone
LSLV
last subject last visit
MACE
major adverse cardiovascular events
MCH
mean corpuscular hemoglobin
MCHC
mean corpuscular hemoglobin concentration
MCV
mean corpuscular volume
N/A
not applicable
PCD
primary completion date
PD
pharmacodynamic
PI
principal investigator
PK
pharmacokinetic(s)
PSA
Prostate Specific Antigen
PT
prothrombin time
QTc
corrected QT
qual
qualitative
RBC
red blood cell
SAE
serious adverse event
SAP
statistical analysis plan
SDV
Single Dose Vial
SOP
standard operating procedure
SRSD
single reference safety document
STOD
Study Team On Demand
t½
terminal elimination half-life
TBili
total bilirubin
THC
tetrahydrocannabinol
ULN
upper limit of normal
US
United States
USPI
United States Prescribing Information
WBC
white blood cell
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