Clinical trial NCT04523480
Conditions: Hypogonadism
Keywords: Low T Low Testosterone
Sponsor: University of Miami
Start date: 2020-03-12; Completion date: 2022-12-20
Enrollment: 75 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate changes in vascular parameters in subjects receiving Testopel 75mg (one time) versus subjects receiving Compounded Testosterone pellets 100mg (one time) versus subjects receiving Compounded Testosterone pellets 200mg (one time) to participant with clinical hypogonadism.

Detailed description:
Hypogonadism, or low testosterone (Low T), is the deficiency in producing testosterone by the testes. Testosterone pellets is a long-acting formulation of Testosterone Replacement Therapy (TRT) that is delivered subcutaneously to men diagnosed with low T. Advantages to subcutaneous testosterone pellets include ease of delivery and decreased risk of the medication being transfer upon skin contact to woman or children. Long acting testosterone replacement Implantation of six to ≥10 testosterone pellets (450 to ≥750 mg) increased total testosterone into the therapeutic range at 1 month post-implantation and sustained therapeutic levels (\>300) for 4-6 months.

Participants will be randomly assigned to 1 of 3 study groups. In one of the groups the treatment will include implantation of Testopel ® 750mg (10 pellets with 75mg pellet) one time, in the second group, treatment will include compounded subcutaneous testosterone 800mg (8 pellets with 100mg pellet) one time and in the third group, treatment will include compounded subcutaneous testosterone 800mg (4 pellets with 200mg pellet) one time.

The treatment takes approximately 30 minutes and will include: Clean and numb the insertion site with lidocaine at 1%, followed by small incision in the skin, implantation of pellets into subdermal fat layer and sealing the incision with Steri-strip. This is the current standard of care of Testopel insertion and same procedure will be followed with both compounded and commercial pellets.

Arms: arm 1: Participants in this group will receive a one-time subcutaneous testosterone insertion of 10 x 75 mg pellets of Testopel for a total of 750 mg Testopel. arm 2: Participants in this group will receive a one-time subcutaneous testosterone insertion of 8 x 100 mg compounded testosterone for a total of 800 mg compounded testosterone. arm 3: Participants in this group will receive a one-time subcutaneous testosterone insertion of 4 x 200 mg compounded testosterone for a total of 800 mg compounded testosterone.
Interventions: intervention 1: Testopel 75mg Drug Implant intervention 2: Testopel 100mg Drug Implant intervention 3: Testopel 200mg Drug Implant
Intervention descriptions: intervention 1: 75 mg Testosterone pellets administered subcutaneously. intervention 2: 100 mg Testosterone pellets administered subcutaneously. intervention 3: 200 mg Testosterone pellets administered subcutaneously.

Protocol documents:
Prot_SAP_000.pdf: 
Version 1.0
Date:  Feb 26, 2019
 IRB# 20190906
Randomized Control Trial of Long Acting Subcutaneous 
Testosterone Pellets for Hypogonadism: Testopel ® vs. Generic 
Testosterone Pellets.
______________________________________________________________________________
PRINCIPAL INVESTIGATOR
SUB-INVESTIGATOR
STUDY COORDINATOR:
NCT#
SPONSOR:
Ranjith Ramasamy, M.D
Assistant Professor
Department of Urology
1120 N.W. 14th St #1560
Miami, Florida 33136
Phone: 305-243-4562
Email: Ramasamy@miami.edu
Libert Ramos, DNP, MSN/Ed, APRN 
Department of Urology
1120 N.W. 14th st #1560
Miami, Florida 33136
Phone: 305-243-4562
Email: Libert.Ramos@miami.edu
Manuel Molina, MD
305-243-4873
Clinical research Coordinator 
Email: m.molina.leyba@miami.edu
NCT04523480
Empower Pharmacy 
Houston, TX 


Version 1.0
Date:  Feb 26, 2019
 IRB# 20190906
Randomized Control Trial of Long Acting Subcutaneous 
Testosterone Pellets for Hypogonadism: Testopel ® vs. Generic 
Testosterone Pellets.
______________________________________________________________________________
PRINCIPAL INVESTIGATOR
Ranjith Ramasamy, M.D
Assistant Professor
Department of Urology
1120 N.W. 14th St #1560
Miami, Florida 33136
Phone: 305-243-4562
Email: Ramasamy@miami.edu
        
SUB-INVESTIGATOR
Libert Ramos, DNP, MSN/Ed, APRN
Department of Urology
1120 N.W. 14th st #1560
Miami, Florida 33136
Phone: 305-243-4562
Email: Libert.Ramos@miami.edu
STUDY COORDINATOR:
Manuel Molina, MD
305-243-4873
Clinical research Coordinator
Email: m.molina.leyba@miami.edu
SPONSOR:
Empower Pharmacy 
Houston, TX 
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Table of Contents
1.BACKGROUND.........................................................................................................................6
1.1
Study Disease ..............................................................................................................................6
1.2
Study Interventions ....................................................................................................................6
1.3
Study Rationale...........................................................................................................................6
2. HYPOTHESIS ...........................................................................................................................7
2.1 Alternate hypothesis..........................................................................................................................7
2.2 Null Hypothesis..................................................................................................................................7
3. OBJECTIVES............................................................................................................................7
3.1 Primary Efficacy Objective ..............................................................................................................7
3.2 Secondary Efficacy Objective...........................................................................................................7
4. STUDY DESIGN .......................................................................................................................7
4.1 Accrual goal .......................................................................................................................................7
4.2 Duration of Study Participation.......................................................................................................8
5 STUDY ENTRY, ENROLLMENT AND WITHDRAWAL...................................................8
5.1 Study Entry ........................................................................................................................................8
5.2 Enrollment Procedure.......................................................................................................................8
5.3 Cancellation Guidelines ....................................................................................................................8
6. PATIENT SELECTION/ELIGIBILITY CRITERIA............................................................9
6.1 Inclusion (Eligibility) Criteria..........................................................................................................9
6.2 Exclusion (Eligibility) Criteria .........................................................................................................9
6.3 Study Population .............................................................................................................................10
7. STUDY DESIGN, CLINICAL, RADIOLOGICAL, LABORATORY AND SURGICAL 
EVALUATIONS..........................................................................................................................11
7.1 Study Design.....................................................................................................................................11
7.2 Screening Evaluations and Procedures .........................................................................................11
7.3 Pre-Treatment Procedures and Evaluations.................................................................................11
7.4 Follow-Up Procedures and Evaluations:.......................................................................................11
    7.5 Reimbursement……………………………………………………………………………11 
8. ADVERSE EVENTS ...............................................................................................................11
8.1 Expected Adverse Events................................................................................................................12
8.2 Serious Adverse Events...................................................................................................................12
9. DATA AND SAFETY MONITORING PLAN .....................................................................12
10. STATISTICAL CONSIDERATIONS.................................................................................12
10.1 Primary Study Endpoints .............................................................................................................12
10.2 Endpoint definitions ......................................................................................................................13
10.3 Sample size, accrual and study duration.....................................................................................13
10.4 Statistical Analysis and Power calculation..................................................................................13
11. INVESTIGATORS RESPONSIBLITIES...........................................................................13
11.1 Investigator Responsibility/Performance....................................................................................13
11.3 Confidentiality ...............................................................................................................................13
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11.4 Informed Consent and Permission to Use Protected Health Information ...............................14
11.5 Source Documentation and Investigator Files............................................................................14
11.6 Recording and Processing of Data ...............................................................................................15
11.7 Non-Protocol Research .................................................................................................................15
11.8 Ethics ..............................................................................................................................................15
11.9 Essential Documents for the conduct of a clinical trial..............................................................15
12. STUDY CALENDAR ............................................................................................................16
13 REFERENCES .......................................................................................................................17
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Investigator’s Statement
This clinical trial shall be conducted in compliance with the protocol, as referenced herein, and all 
applicable local, national, and international regulatory requirements to include, but not be limited 
to:
·
International Conference on Harmonization (ICH) Guidelines on Good Clinical Practice 
(GCP)
·
Ethical principles that have their origins in the Declaration of Helsinki 
·
Food and Drug Administration (FDA) Code of Federal Regulation (CFR):
o
Title 21CFR Part 50 and 45 CFR Part 46, Protection of Human Patients
o
Title 21CFR Part 54, Financial Disclosure by Clinical Investigators
o
Title 21CFR Part 56, Institutional Review Boards
o
Title 45 CFR Parts 160, 162, and 164, Health Insurance Portability and 
Accountability Act (HIPAA)
As the Principal Investigator, I understand that my signature on the protocol constitutes my 
agreement and understanding of PI responsibilities to conduct the clinical trial in accordance to 
the protocol and applicable regulations.  Furthermore, it constitutes my understanding and 
agreement that any changes initiated by myself, without prior agreement in writing from the 
Sponsor, shall be defined as a deviation from the protocol, and shall be formally documented as 
such.
I understand that my signature constitutes agreement and understanding of acceptance of the 
defined responsibilities of a Sponsor-Investigator as defined by the protocol, applicable FDA 
Regulations, and/or business contracts, but does not in any capacity relieve me of my 
responsibilities as the Sponsor-Investigator.  Additionally, my signature constitutes my 
understanding and agreement that any changes to the protocol shall be implemented timely with 
my review and approval prior to implementation.
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INVESTIGATOR'S AGREEMENT
I confirm that I have read this protocol, I understand it, and I will work according to this protocol 
and to the ethical principles stated in the latest version of the Declaration of Helsinki, the applicable 
ICH guidelines for good clinical practices, and the applicable federal, state, and local laws, rules, 
and regulations relating to the conduct of the protocol.  
I have read and understand the information in the Instructions for Use (and/or other such pertinent 
safety information) regarding the risks and potential benefits.  
I agree to inform all those who assist/collaborate with me in the conduct of this study of their 
responsibilities and obligations. 
Once the protocol has been reviewed and approved by the Institutional Review Board (IRB) I 
understand that any change(s) made during the course of the study must also (first) be approved 
by the IRB prior to implementation, except when such modification is made to remove any 
immediate hazard(s) to the subject(s).  
I certify that I, and the study staff responsible, have received the requisite training to conduct this 
research protocol.  
I agree to maintain adequate and accurate records in accordance with the University of Miami 
policies, federal, state and local laws and regulations.  
I agree to maintain the confidentiality of all information received and/or developed in connection 
with this protocol.
Ranjith Ramasamy
Print Name of Physician
March 1st, 2019
Physician’s Signature
Date
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1.BACKGROUND
1.1 Study Disease
Administration of exogenous testosterone as efficacious treatment for male hypogonadism has been 
part of medical practice for more than 50 years. Testosterone is an anabolic steroid and the primary 
male sex hormone promoting development of male reproductive tissues such as prostate and testis. 
Several androgen replacement modalities are FDA approved and commercially available or are under 
clinical investigation. These include intramuscular injection of testosterone esters, subcutaneous 
implants, transdermal patches, oral tablets and capsules, buccal and sublingual dosage forms, 
implantable T microspheres, and topical gel formulations of testosterone and 5α-dihydrotestosterone 
(DHT).
 It can activate androgen receptors in its unchanged form or it can be converted to 5α-
dihydrotestosterone (DHT) by the enzyme 5 α reductase before binding to the androgen receptor. 
Once bound, the receptor-hormone complex moves into the cell nucleus altering specific gene 
sequences on the cellular DNA and modifying its transcription, therefore promoting protein 
synthesis and thus growth of tissues that are sensible to its action.1    
Hypogonadism, or low testosterone (Low T), is the deficiency in producing testosterone by the 
testes. Low T affects more than 10% of men worldwide, with high incidence in the elderly (Haring, 
et al., 2010). It occurs in association with aging, chronic disease, or other modifiable risk factors 
such as obesity and diabetes.1 Testosterone deficiencies have been shown to associated with less 
muscle mass3, lower bone mineral density4, lower hematocrit and hemoglobin concentrations5, 
smaller prostate glands6, and diminished energy and sexual function than normal men.7,8
1.2 Study Interventions
Testosterone replacement therapy (TRT) is becoming more widely available and has seen a greater 
than three-fold increase in use men 40 years and older.9 Current delivery systems of TRT include 
transdermal gels and patches10, injection therapy11, and long acting subcutaneous pellets.12 TRT 
has been shown to improve bone mineral density, prostate volume, energy, and sexual function.8 
Testosterone pellets is a long-acting formulation of TRT that is delivered subcutaneously to men 
diagnosed with low T. This method of administration has the potential to avoid side effects related 
to TRT that are commonly seen with other delivery methods, daily topical applications present a 
risk of transfer of testosterone to partners and family members as well as a short half-life of 
injectable and intranasal products. A recent study showed that this medication is well tolerated 
with very low adverse events and discontinuation rates among patients. 11
Treatment was well tolerated; adverse event rates were
low. Adverse event discontinuation rates were 2.1% (b.i.d.) and 3.7% (t.i.d.)
Treatment was well tolerated; adverse event rates were
low. Adverse event discontinuation rates were 2.1% (b.i.d.) and 3.7% (t.i.d.)
1.3 Study Rationale 
Current advantages to subcutaneous testosterone pellets include ease of delivery and decreased 
risk of the medication being transfer upon skin contact to woman or children.11 Long acting 
testosterone replacement Implantation of six to ≥10 testosterone pellets (450 to ≥750 mg) increased 
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total testosterone into the therapeutic range at 1 month post-implantation and sustained therapeutic 
levels (>300) for 4-6 months. Higher pellet numbers (10-12 pellets) were associated with higher, 
more consistent, and longer maintenance of testosterone levels within the therapeutic range. 
Our hypothesis Pellets provide sustained eugonadal T levels for 3–6 months with not significant 
difference between Testopel ® and compound subcutaneous testosterone. 
2. HYPOTHESIS
2.1 Alternate hypothesis
Treatment groups will show a sustainable testosterone value between 300ng/dl and 1000 ng/dl 
from baseline in patients with low T, to 6 months post-therapy. 
2.2 Null Hypothesis
There is no difference between the patient receiving Testopel ® vs Subcutaneous compound 
testosterone pellets. 
3. OBJECTIVES
3.1 Primary Efficacy Objective
Primary outcomes will be changes in Testosterone (T) from baseline, 2 month, 4 month and 6 
month.
3.2 Secondary Efficacy Objective
We will evaluate changes in Hematocrit (HCT), Estrogen (E) and PSA from baseline to 2 month, 
4 month and 6 months.
4. STUDY DESIGN
4.1 Accrual goal
A total of 120 patients with low testosterone (<300ng/dL) on 2 measurements meeting the 
eligibility criteria will be recruited from the Department of Urology clinic. 
4.2 Duration of Study Participation
Total study duration will be 6 months (180 days) and subjects will be provided subcutaneous 
testosterone one time.  Implantation of Testopel ® 750 mg (10 pellets with 75mg pellet) or 
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compounded subcutaneous testosterone 800mg (8 pellets with 100mg pellet) or compounded 
subcutaneous testosterone 800mg (4 pellets with 200mg pellets). 
5. STUDY ENTRY, ENROLLMENT AND WITHDRAWAL
5.1 Study Entry
Study entry, as used in this protocol, will be defined as a subject signing informed consent.  Study 
enrollment, as used in this protocol, will be defined as the investigator’s confirmation of the 
subject’s eligibility by signing an eligibility checklist.  As per University of Miami policy, each 
study participant, including participants who have screened failed, who sign an informed consent 
form, should be entered into the study database. 
5.2 Enrollment Procedure
Completed and signed protocol-specific eligibility checklist; 
All pages of the original signed informed consent forms (ICFs), including HIPAA Form B; 
Relevant source documents or medical records such as:  subject medical history and physical 
exam, admission or discharge notes, diagnostic reports, pathologic confirmation of diagnosis, and 
relevant subject-specific written communication.
Documentation from the Investigator that he/she has determined the subject meets eligibility 
criteria. 
5.3 Cancellation Guidelines
The following are reasons for withdrawal of subjects from the study:
A subject does not meet the eligibility criteria; (the subject will be considered a screen 
failure).  
A subject withdraws consent, 
A subject dies during protocol participation from causes other than the study treatment 
(not due to adverse events) or 
A study investigator decides the subject should be withdrawn from the study (e.g. 
subject non-compliance) 
Regardless of reason for withdrawal, an intention to treat analysis will be performed. 
All subjects who either screen fails, is withdrawn from the study or has completed all visits should 
be de-enrolled from the research database within 48 hours.  
6. PATIENT SELECTION/ELIGIBILITY CRITERIA
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6.1 Inclusion (Eligibility) Criteria
Subjects must meet the following criteria:
1. Voluntarily sign and date the study consent form(s), which have been approved by an 
Institutional Review Board (IRB). Written consent must be obtained prior to the 
initiation of any study procedures. 
2. Male between 18 and 75 years of age.  
3. Documented diagnosis of primary hypogonadism (congenital or acquired) or 
hypogonadotropic hypogonadism (congenital or acquired).
4. Serum total testosterone < 300 ng/dL on 2 measurements 
5. Naïve to androgen replacement or has discontinued current treatment and completed a 
washout of 4 weeks following androgen treatment. 
6. Judged to be in good general health as determined by the principal investigator based 
upon the results of a medical history, physical examination, vital signs, laboratory 
profile and a 12-lead electrocardiogram (ECG).
6.2 Exclusion (Eligibility) Criteria
Subjects meeting any of the following criteria will be excluded from the study:
1. History of significant sensitivity or allergy to androgens, or product excipients.
2. Clinically significant findings in the pre-study examinations including abnormal breast 
examination requiring follow-up, abnormal ECG. 
3. Abnormal prostate digital rectal examination (DRE) with palpable nodule(s) or I-PSS 
score > 19 points. 
4. Body mass index (BMI) ≥ 40 kg/m2. 
5. Clinically significant abnormal laboratory value, in the opinion of the investigator, in 
serum chemistry, hematology, or urinalysis including but not limited to: 
a. Baseline hemoglobin > 16 g/dL 
b. Hematocrit < 35% or > 50% 
c. PSA > 4 ng/mL 
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6. History of seizures or convulsions, including febrile, alcohol or drug withdrawal 
seizures. 
7. History of any clinically significant illness, infection, or surgical procedure within 4 
weeks prior to study drug administration.
8. History of stroke or myocardial infarction within the past 5 years. 
9. History of, or current or suspected, prostate or breast cancer. 
10. History of diagnosed, severe, untreated, obstructive sleep apnea. 
11. History of abuse of alcohol or any drug substance in the opinion of the investigator 
within the previous 2 years. 
12. Donation or loss of 550 mL or more blood volume (including plasmapheresis) or receipt 
of a transfusion of any blood product within 12 weeks prior to the start of treatment. 
13. Inadequate venous access for collection of serial blood samples required for 
pharmacokinetic profiles. 
14. Receipt of any investigational product within 4 weeks or within 5 half-lives prior to the 
start of treatment. 
15. Inability to understand and provide written informed consent for the study. 
6.3 Study Population
The study will consist of 120 males suffering from low testosterone .
6.4 Setting
Subjects will be identified from those visiting the University of Miami – Department of Urology 
and the UHealth Fertility Center, and receiving the diagnosis of idiopathic hypogonadism. If they 
meet the inclusion criteria, the patients will receive an explanation of the study. Patients will be 
informed both verbally and in written form of the study and procedures involved. The PI, Resident, 
Fellows and/or the study coordinator will obtain a signed/dated Informed Consent Document 
(ICD) before enrolling each subject. Subsequent visits will take place in the same Clinic. Study 
data will be safely stored in a RedCap database. 
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7. STUDY DESIGN, CLINICAL, RADIOLOGICAL, LABORATORY AND SURGICAL 
EVALUATIONS
7.1 Study Design 
This is a prospective, Phase 3, randomized, clinical study aimed to evaluate comparison between 
Testopel ® vs subcutaneous compounded testosterone for men with low testosterone. Subjects will 
be enrolled in the study based on selection criteria designed to represent the general population of 
hypogonadal men while minimizing risk to study participants. Approximately 120 subjects will be 
enrolled to meet scientific and regulatory objectives. After meeting the selection criteria, the 
subjects will be randomly assigned in 1:1:1 ratio such that 40 subjects will receive Testopel,  40 
subjects will receive Compounded testosterone pellets  (8 pellets with 100mg pellets) once and 40 
subjects will receive compounded testosterone pellets (4 pellets with 200mg pellets) once and will 
be followed for 6 months. Subjects may be naive to testosterone treatment or may enroll after 
stopping current treatment and completing an adequate washout period. 
7.2 Screening Evaluations and Procedures
The first visit of the patients will be for screening and medical evaluation. Patient’s medical co-
medication history will be collected and documented and a physical examination will be 
performed. 
Previous month’s blood test results will be reviewed including a general chemistry panel and 
Testosterone levels during chart review.
Patients will sign an informed consent and in case they meet all inclusion criteria (and do not meet 
any exclusion criteria), they will be recruited to the study. 
7.3 Pre-Treatment Procedures and Randomization
The results of all screening evaluations must be within clinically acceptable limits, reviewed and 
approved by the investigator, prior to the start of treatment. Subjects who meet the inclusion 
criteria and do not meet any of the exclusion criteria may proceed to randomization. A central 
randomization scheme will be used. To allow subjects in screening once the target 120 subjects 
have been enrolled and to account for dropouts, 145 randomization codes will be generated. As 
subjects are enrolled in the study, they will be assigned unique consecutive numbers starting at 
001. At least 120 subjects who meet all the entry criteria will be randomized 1:1:1 such that 
approximately 40 subjects are assigned to the Testopel treatment arm,  approximately 40 subjects 
are assigned to the Compounded treatment arm (100mg pellets) and 40 subjects are assigned to 
the Compounded treatment arm (200mg pellets),  (Randomization will be performed by a 
computer software maintained by the Department of Urology). Patients randomized to the 
treatment group will be instructed to stop any use of androgen replacement therapy for 4 weeks 
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prior to first treatment session and refrain from using any other testosterone therapy option during 
the study. 
7.4 Treatment procedures
Clean and numb the insertion site with lidocaine at 1%, followed by small incision in the skin, 
implantation of pellets into subdermal fat layer and sealing the incision with Steri-strip. This is the 
current standard of care of Testopel insertion and same procedure will be followed with both 
compounded and commercial pellets. 
7.5 Follow-Up Procedures and Evaluations:
Follow-up visits will be conducted at 2, 4. 6 months, these visits shall include: 

Taking serum T, HCT, E, PSA levels. 

Reporting and recording adverse events at every follow-up visit.
7.6 Reimbursement 
Once the patient is included into the trial, the sponsor company (Empower pharmacy) will 
reimburse $75 for participation. Once randomized, the sponsor company (Empower Pharmacy) 
will provide one time treatment “Testopel or Compounded Testosterone” based on the results of 
randomization.  
8. ADVERSE EVENTS
8.1 Expected Adverse Events 
The following adverse reactions have been identified during post-approval use of testosterone 
replacement therapy, including TESTOPEL®. Including implantation site infection and pellet 
extrusion, gynecomastia, oligospermia, hirsutism, male pattern of baldness, and acne.  
Cardiovascular disorders as myocardial infarction, stroke. Fluid and electrolyte disturbances, 
increased or decreased libido, headache, anxiety, or depression. Metabolic increased serum 
cholesterol.
8.2 Serious Adverse Events 
Serious injury or death 
Any adverse event and eventual complication must be recorded at any time during the treatments 
and the follow up visits, and throughout the entire study duration. Patients will be instructed to 
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alert the study investigator by telephone of any side effects occurring in the period after the 
treatment and until the study end. 
9. DATA AND SAFETY MONITORING PLAN
The study investigators will report to a surgeon monitor Dr. Ramgopal Satyanarayana in the 
department of urology (who is not involved in the study) to ensure data quality and subject safety. 
The investigators will conduct continuous reviews of the data and subject safety; keeping track of 
the number of subjects, significant toxicities in accordance with the protocol and observed 
responses, which will be discussed at research committee meetings. All grade 3-5 adverse events 
(CTCAE v4.0), regardless of association with the subcutaneous testosterone, will be entered into 
study database and reviewed at research committee meetings. In addition, all adverse reactions 
considered “serious”, will be entered into the research database and reviewed by the Surgeon 
monitor on an ongoing basis. If a death occurs within 30 days of subcutaneous testosterone 
implantation treatment and is determined to be related to the study, the investigators will notify 
the Department Chair Dr. Dipen Parekh within 1 business day. If an increase in the frequency of 
grade 3 or 4 adverse events is noted in the study, a report will be submitted to the Department 
Chair Dr. Dipen Parekh at the time the increased rate is identified. If at any time the principal 
investigator stops enrollment or stops the study due to safety issues, the Department Chair (Dr. 
Dipen Parekh) will be notified within 1 business day and a formal letter will be sent to the 
Department Chair (Dr. Dipen Parekh) to be received within 10 business days. Additionally to 
reporting to the Department chair, all serious events will also be reported to the supervising IRB 
in the same timely manner. 
10. STATISTICAL CONSIDERATIONS
10.1 Primary Study Endpoints
The primary endpoint will be change in T, after 6 months of treatment. 
The primary endpoint will be the change in T, post-treatment subjects who achieve an average serum 
T concentration within the normal range upon completion of 24 weeks of post- treatment. 
10.2 Secondary Study Endpoints
The secondary endpoints will be changes in HCT, ESTROGEN and PSA, after 6 months of 
treatment
10.3 Endpoint definitions
Total testosterone will be expressed in ng/dL, HCT(%), E (pg/ml), and PSA ng/ml  Hormone 
determinations will be done by peripheral venous puncture blood draw. 
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10.4 Sample size, accrual and study duration
TOTAL SAMPLE SIZE: 120
TOTAL ACCRUAL: 120
ACCURAL DURATION: 12 months
STUDY DURATION: 6 months
10.5 Statistical Analysis and Power calculation  
The average and standard deviation of all relevant variables and baseline characteristics, primary 
and secondary outcomes will be calculated. 
Change in Testosterone, Hematocrit, estrogen and PSA will be analyzed using the ANOVA and 
MANOVA. A change in < ± 10% will be reject the null hypothesis.
Demographic characteristics such as age and testosterone level will be compared between groups 
A and B using student's test. Other demographic characteristics, such as medical background and 
risk factors will be compared between these groups using Fisher's exact test.
10.6 Randomization:
120 patients will be randomized 1:1:1 to Testopel ® vs compound groups with 40 patients in the 
Testopel ® arm ,  40 patients in the compounded pellets arm (100mg) and 40 patients in the 
compounded pellets arm (200mg)  . An online-based randomization tool called Redcap.com will 
be used. The PI will not have the knowledge of patient’s treatment group beforehand. However, 
the study coordinator will be aware of Testopel vs compound group randomization. 
11. INVESTIGATORS RESPONSIBLITIES
11.1 Investigator Responsibility/Performance
The investigator (or a person designated by the investigator) should inform the patient of all 
pertinent aspects of the study, including the written information.
The investigator should provide the patient ample time and opportunity to inquire about details of 
the study and to decide whether to participate in the study or not.  All questions about the study 
should be answered to the satisfaction of the patient. Neither the investigator, nor the study staff, 
should coerce or unduly influence a patient to participate or to continue to participate in a study.
11.3 Confidentiality
The identity of the patients in this study will be treated as confidential. Patients eligible to 
participate in the study following the pre-treatment visit will be assigned a unique patient code. 
The results of the study, including any other data, may be published for scientific purposes but will 
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not give the patients' name or include any identifiable references to them. However, any records 
or data obtained as a result of the patient participation in this study may be inspected by the 
sponsor, by any relevant governmental agency, by the Hospital Ethics Committee, or by the 
persons conducting this study, provided that such inspectors are legally obligated to protect any 
identifiable information from public disclosure, except where disclosure is otherwise required by 
law or a court of competent jurisdiction. These records will be kept private as permitted by law. 
11.4 Informed Consent and Permission to Use Protected Health Information 
It is the responsibility of the investigator to obtain written informed consent from each subject 
participating in this study after adequate explanation, in lay language, of the methods, objectives, 
anticipated benefits, and potential hazards of the study.  The investigator must also explain that 
the subject is completely free to refuse to enter the study or to discontinue participation at any time 
(for any reason) and receive alternative conventional therapy as indicated.  Prior to study 
participation, each subject will sign an IRB approved informed consent form and receive a copy 
of same (and information leaflet, if appropriate). 
The investigator or designee must explain to the subject before enrollment into the study that for 
evaluation of study results, the subject’s protected health information obtained during the study 
may be shared with the study sponsor, regulatory agencies, and the IRB.  It is the investigator’s 
(or designee’s) responsibility to obtain permission to use protected health information per HIPAA 
from each subject, or if appropriate, the subjects’ parent or legal guardian.
11.5 Source Documentation and Investigator Files
The investigator will maintain adequate and accurate records to document the conduct of the study 
and to ensure that study data can be subsequently verified.  These documents will be classified into 
two separate categories: (1) investigator study file and (2) subject clinical source documents that 
corroborate data collected on the CRF’s.  Subject clinical source documents would include 
hospital/clinic patient records; physician's and nurse's notes; original laboratory, radiology, 
pathology, and special assessment reports; QOL forms, signed informed consent forms.  When the 
CRF or any form is used as the source document, this will be clearly stated in the investigator 
study file.
At a minimum, the following be documented in source documents:

Medical history/physical condition and diagnosis of the subject before involvement 
in the study sufficient to verify protocol entry criteria.

Study number, assigned subject number, and verification that written informed 
consent was obtained (each recorded in dated and signed notes on the day of entry 
into the study)

Progress notes for each subject visit.

Laboratory test results.
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
Condition and response of subject upon completion of or early termination from 
the study.
11.6 Recording and Processing of Data
Data for this study will be entered into electronic CRFs in research database (a web-based clinical 
research management application).  A CRF is required for every patient who received any study 
intervention.  The investigator will ensure that the CRF’s are accurate, complete, legible and 
timely. Separate source records are required to support all CRF entries.  All corrections to study 
data will be made by drawing a single line through the information to be corrected without 
obscuring it.  All corrections will be initialed, dated, and explained, if necessary. Do not use 
“white-out” or obscuring correction tape.  
11.7 Non-Protocol Research
No investigative procedures other than those described in this protocol will be undertaken on the 
enrolled subjects without the agreement of the IRB.
11.8 Ethics
The investigator agrees to conduct the study in compliance with the protocol, current good clinical 
practices, and all applicable (local, FDA) regulatory guidelines and standard of ethics
11.9 Essential Documents for the conduct of a clinical trial
Essential documents are those documents with individually and collectively permit evaluation of 
the conduct of a trial and the quality of the data produced.
The following documents will be on file:

CV’s and license of all investigators.

IRB documentation/correspondence.

Documentation of IRB certification.
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12. STUDY CALENDAR
          Visit #, Time
Activity
Visit 1 
(1st month)
Screening
Visit 2 
(Week 2)
Visit 3 
(Week 6)
Visit 4 
(Week 14)
Visit 5 
(Week 22) 
Visit 6 
(Week 24) 
Visit 7 
(Week 26)
Medical 
& 
Urological History
●
●
Physical 
Examination 
●
●
Informed Consent
●
Randomization
●
Inclusion & 
Exclusion Criteria
●
Blood Analysis ( T, 
E, HCT, PSA)
●
●
●
●
●
Subcutaneous 
testosterone 
therapy in-office 
insertion
(CPT 11980)
●

Pellets will be provided by sponsor 

Laboratory visits at LABCORP on Visit 3, 4, 5 and 6 will be covered by the 
sponsor with a separate account provided by sponsor 
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