CYP19A1 (Cytochrome P450 Family 19 Subfamily A Member 1) Gene and Pharmacogenetics of Response to Testosterone Therapy

• Sponsor: VA Office of Research and Development (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT01378299
• Collaborator: Baylor College of Medicine (Other)
• Enrollment: 105
• Locations: 2
• Arm: 1
• Actual Duration (Months): 73.2
• Patients Per Site: 52.5
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

Testosterone (T) replacement prevents bone loss and relieves symptoms associated with androgen deficiency in male patients with hypogonadism, but at the expense of an increase in prostate-related adverse events and in the hematocrit values above the normal which may lead to bad circulatory outcomes. Most of the effects of T on the male skeleton are mediated by its conversion to estradiol (E2) by the enzyme aromatase. Genetic variations in the aromatase (CYP19A1) gene result in enzymes with variable activity and variable levels of E2 and T. This project is designed to determine if genetic variations in the CYP19A1 gene will result in differences in the skeletal response and incidence of side effects from T treatment in patients with low T. A large number of male Veterans are on T. Results from this project will help identify patients who would benefit from the therapy from those at risk for side effects, and would definitely have an impact in the future care of these patients and male patients in general once genetic profiling becomes part of the standard of care.

Condition or Disease	Intervention/Treatment	Phase
Hypogonadism	Drug: Testosterone Cypionate	Phase 1

Detailed Description

Estrogen has been gaining recognition as the primary hormone that regulates the male skeleton. Estrogen in males is mainly derived from the conversion of testosterone to estradiol by the enzyme aromatase. Polymorphisms of the aromatase gene (CYP19A1) have been reported to result in variable enzyme activity resulting in variable hormonal profile and differences in bone mineral density (BMD) among the variants. These polymorphisms were also found to influence changes in BMD in response to hormone therapy in postmenopausal women and bone loss from aromatase inhibitors in women with breast cancer. It is possible that these same polymorphisms will also influence skeletal response to testosterone therapy in hypogonadal males given testosterone.

Among the side effects described for testosterone therapy, prostate-related events and an increase in hematocrit represent as the more common and the potentially more serious side effects. However, these side effects do not affect everybody, suggesting that a certain subgroup of patients is predisposed to these side effects. Because polymorphisms in the CYP19A1 gene result differences in activity among variants leading in variable substrate and product accumulation, the investigators hypothesize that these polymorphisms will influence the skeletal response and perhaps susceptibility to side effects from testosterone therapy. Thus the objectives of this proposal are: (1) To evaluate the influence of polymorphisms in the CYP19A1 gene on the skeletal response to testosterone in male patients with low testosterone, (2) To evaluate the influence of polymorphisms in the CYP19A1 gene on the susceptibility to side effects from testosterone therapy, (3) To evaluate the changes in functional activity of the aromatase enzyme in clinically significant CYP19A1 gene polymorphisms. The investigators propose to treat 105 patients with testosterone cypionate 200 mg IM every 2 weeks for an 18-month treatment period. The investigators will do serial measurements of BMD by dual energy X-ray absorptiometry, markers of bone turnover, hematocrit, prostate-specific antigen (PSA), prostate volume and hormonal assays. Changes in BMD and markers of bone turnover with testosterone treatment will be compared among the different CYP19A1 genotypes. The investigators will also compare changes in hematocrit, PSA and prostate volume among the different CYP19A1 genotypes. Changes in functional activity among the variants will be evaluated by CYP19 gene expression studies on the adipose tissues obtained from periumbilical fat biopsies, and by changes the in estradiol to testosterone ratio, a surrogate marker for aromatase activity. The investigators anticipate that variants with increase in activity will have relatively higher estradiol levels than less active variants resulting in greater increments in BMD. Meanwhile, less active variants will have relatively higher levels of testosterone than other variants and have greater increments in hematocrit. On the other hand, variants associated with higher estradiol to testosterone ratio will experience greater increases in PSA and prostate volume with therapy.

The incidence of testosterone deficiency goes up with aging and the presence of co-morbid conditions making male hypogonadism one of the common problems among patients attending the VA clinics who, are for the most part, elderly with various co-morbid conditions. Indeed, a large number of VA patients are already taking testosterone for hypogonadism, some of them primarily to prevent further bone loss. It is possible that some of these patients do not derive benefit from the drug while subjecting them to potential serious side effects. Results from this proposal will identify the genetic profiles of favorable responders from poor responders or those who might be more prone to serious side effects, thus, may impact the future care of male Veterans and hypogonadal patients in general, once genetic profiling becomes part of the standard of care.

Study Design

• Study Type: Interventional
• Actual Enrollment: 105 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: CYP19A1 Gene and Pharmacogenetics of Response
• Actual Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Nov 7, 2016
• Actual Study Completion Date: Nov 7, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Arm 1: Testosterone Cypionate All patients who qualify for the study will receive testosterone cypionate

Drug: Testosterone Cypionate; Testosterone cypionate was administered at 200 mg by intramuscular injection every 2 weeks. DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. It is insoluble in water, freely soluble in alcohol, chloroform, dioxane, ether, and soluble in vegetable oils. The chemical name for testosterone cypionate is androst-4-en-3-one,17-(3-cyclopentyl-1oxopropoxy)-, (178)-. Its molecular formula is CvH400a, and the molecular weight of 412.61.; Other Names: depo testosterone

Outcome Measures

Primary Outcome Measures

1. Percent Change in Bone Mineral Density (BMD) According to rs700518 Polymorphism in the CYP19A1 Gene [form baseline to 18 months]

   Percent change in bone mineral density from baseline to 18 months

2. Percent Change in Bone Mineral Density (BMD) According to the rs1062033 Polymorphism in the CYP19A1 Gene [baseline to 18 months]

   Percent change in bone mineral density from baseline to 18 months.

Secondary Outcome Measures

1. Percent Change in Bone Mineral Density According to Body Mass Index (BMI) [baseline to 18 months]

   Percent changes in bone mineral density from baseline

2. Percent Change in Prostate-specific Antigen (PSA) According to the rs700518 Polymorphism of the CYP19A1 Gene [From baseline to 18 months]

   Percent change in PSA from baseline to 18 months

3. Percent Change in Prostate-specific Antigen (PSA) According to the rs1062033 Polymorphism of the CYP19A1 Gene [from baseline to 18 months]

   Percent change in PSA from baseline at 18 months

4. Percent Change in Hematocrit According to the Genotype of the 700518 Polymorphism of the CYP19A1gene [baseline to 18 months]

   Percent change in hematocrit from baseline to 18 months

5. Percent Change in Hematocrit According to re1062033 Polymorphism of the CYP19A1 Gene [Baseline to 18 months]

   Percent change in hematocrit from baseline to 18 months

6. Percent Change in Aromatase Gene Activity From the Buffy Coat According to the 700518 Polymorphism of the CYP19A1 Gene [Baseline to 6 months]

   Percent change in gene expression from baseline to 18 months

7. Percent Change in Bone Turnover Markers According to the rs700518 Polymorphism of the CYP19A1 Gene [Baseline to 18 months]

   Percent change in bone turnover from baseline to 18 months.

8. Percent Change in Bone Turnover Markers According to the rs1062033 Polymorphism of the CYP19A1 Gene [Baseline to 18 months]

   Percent change in bone turnover markers

9. Percent Change in Bone Mineral Density According the Presence of Diabetes Mellitus [Baseline to 18 months]

   Percent change in bone mineral density from baseline to 18 months

10. Percent Change in Bone Turnover Markers According the Presence of Diabetes Mellitus [Baseline to 18 months]

    Percent change in bone turnover markers from baseline to 18 months.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 75 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Male Veterans with low total testosterone (<300 ng/dl) as defined by the Endocrine Society, who are between 40-75 years of age.

• These patients must be ambulatory; and be willing and able to provide written informed consent.

Exclusion Criteria:

• history of prostate cancer, breast cancer

• history of testicular disease

• untreated sleep apnea

• any ongoing illness that, in the opinion of the investigator, could prevent the subject from completing the study

• patients with a hematocrit of more than 50% (2010 Endocrine Society Guidelines)

• prostate-related findings of a palpable prostate nodule on exam, a serum PSA of 4.0 ng/ml or more, International Prostate Symptom Score >8(9), urinary postvoid residual by ultrasound of >149 ml, or an abnormal transrectal ultrasound

• patients who are on androgen replacement therapy, selective androgen receptor modulator, or finasteride

• patients currently on medications that affects bone metabolism such as:

• estrogen

• the selective estrogen receptor modulator (SERM) as raloxifene

• use of bisphosphonates (i.e. risedronate, alendronate, zoledronic acid and pamidronate)

• within two years of study entry

• aromatase inhibitors

• GnRH analogs

• glucocorticoids of at least 5 mg daily for one month or more

• anabolic steroids

• dilantin

• warfarin

• patients with diseases known to interfere with bone metabolism as hyperparathyroidism, untreated hyperthyroidism, osteomalacia, chronic liver disease, renal failure, hypercortisolism, malabsorption and immobilization

• those with current alcohol use of more than 3 drinks per day (62).

• history of documented coronary artery disease at high risk for recurrence

• Subjects with osteoporosis or a BMD T-score of -2.5 in the lumbar spine, total femur or femoral neck as well as those patients with a history of osteoporosis-related fractures (spine, hip or wrist) or vertebral deformities on lateral spine radiographs deemed as fragility fractures by the team principal investigator.

• history of documented coronary artery disease at high risk for recurrence, history of deep vein thrombosis and cerebrovascular event.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New Mexico VA Health Care System, Albuquerque, NM	Albuquerque	New Mexico	United States	87108-5153
2	Michael E. DeBakey VA Medical Center, Houston, TX	Houston	Texas	United States	77030

Sponsors and Collaborators

• VA Office of Research and Development
• Baylor College of Medicine

Investigators

• Principal Investigator: Reina C Villareal, MD, New Mexico VA Health Care System, Albuquerque, NM

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT01378299
• Other Study ID Numbers: SPLC-001-10S
• First Posted: Jun 22, 2011
• Last Update Posted: Mar 5, 2019
• Last Verified: Feb 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by VA Office of Research and Development: testosterone
• Additional relevant MeSH terms: Hypogonadism; Methyltestosterone; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate

Study Results

Participant Flow

Arm/Group Title	Arm 1: Testosterone Cypionate
Arm/Group Description	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided into different groups of BMI. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. It is insoluble in water, freely soluble in alcohol, chloroform, dioxane, ether, and soluble in vegetable oils. The chemical name for testosterone cypionate is androst-4-en-3-one,17-(3-cyclopentyl-1oxopropoxy)-, (178)-. Its molecular formula is CvH400a, and the molecular weight 412.61.is available in two strengths, 100 mg/mL and 200 mg/mL testosterone cypionate.
Period Title: Overall Study
STARTED	105
BMI group1	38
BMI Group 2	40
BMI Group 3	27
COMPLETED	74
NOT COMPLETED	31

Baseline Characteristics

Arm/Group Title	Arm 1: Testosterone Cypionate
Arm/Group Description	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided into different groups of BMI. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. It is insoluble in water, freely soluble in alcohol, chloroform, dioxane, ether, and soluble in vegetable oils. The chemical name for testosterone cypionate is androst-4-en-3-one,17-(3-cyclopentyl-1oxopropoxy)-, (178)-. Its molecular formula is CvH400a, and the mole
Overall Participants	105
Age (years) [Mean (Standard Deviation) ]
BMI group 1	61.7 (8.5)
BMI group 2	57.3 (8.7)
BMI group 3	60.0 (7.4)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	38 36.2%
Female	0 0%
Male	40 38.1%
Female	0 0%
Male	27 25.7%
Race/Ethnicity, Customized (Count of Participants)
Caucasians	45 42.9%
Blacks	11 10.5%
Hispanics	33 31.4%
Asian	1 1%
American Indian	1 1%
Not reported	14 13.3%
Region of Enrollment (Count of Participants)
United States	105 100%
Body mass index (kg/m2) [Mean (Standard Deviation) ]
BMI group 1	27.2 (1.9)
BMI group 2	32.1 (1.4)
BMI group 3	39.8 (3.9)
patients with diabetes mellitus (Count of Participants)
patients with diabetes mellitus	49 46.7%
patients without diabetes mellitus	56 53.3%
aromatase activity as assessed using estradiol to testosterone ratio (estradiol to testosterone ratio) [Mean (Standard Deviation) ]
Tertile 1	0.069 (0.04)
Tertile 2	0.25 (0.07)
Tertile 3	1.37 (1.12)

Outcome Measures

1. Primary Outcome

Title	Percent Change in Bone Mineral Density (BMD) According to rs700518 Polymorphism in the CYP19A1 Gene
Description	Percent change in bone mineral density from baseline to 18 months
Time Frame	form baseline to 18 months

Outcome Measure Data

Analysis Population Description

Analysis was by intention to treat with the last value carry forward. Those who had at least one follow-up from baseline were included in the analysis. The data from 84 subjects were available for analysis; 15 in the GG, 44 in the GA and 25 in the AA genotype.

Arm/Group Title	GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene	GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene	AA Genotype for the rs700518 Polymorphism of the CYP19A1 Gene
Arm/Group Description	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided into the different genotypes for the rs700518 polymorphism of the CYP19A1 gene. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. It is insoluble in water, freely soluble in alcohol, chloroform, dioxane, ether, and soluble in vegetable oils. The chemical name for testosterone cypionate is androst-4-en-3-one,17-(3-cyclopentyl-1oxopropoxy)-, (178)-. Its molecular formula is CvH400a, and the mole	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided into the different genotypes for the rs700518 polymorphism of the CYP19A1 gene.	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided into the different genotypes for the rs700518 polymorphism of the CYP19A1 gene.
Measure Participants	15	44	25
Lumbar spine	3.69 (0.87)	4.13 (0.52)	3.82 (0.70)
Total hip	0.38 (0.93)	0.93 (0.49)	0.08 (0.66)
Femoral neck	-1.09 (1.28)	1.51 (0.69)	-1.25 (0.91)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene, GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene
	Comments	Analysis by intention to treat with last value carry forward.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANOVA
	Comments

2. Primary Outcome

Title	Percent Change in Bone Mineral Density (BMD) According to the rs1062033 Polymorphism in the CYP19A1 Gene
Description	Percent change in bone mineral density from baseline to 18 months.
Time Frame	baseline to 18 months

Outcome Measure Data

Analysis Population Description

Analysis was by intention to treat with the last value carry forward. Those who had at least one follow-up from baseline were included in the analysis . The data of 82 subjects were available for analysis; 14 in the GG, 38 in the GC and 32 in the CC genotype.

Arm/Group Title	GG Genotype of the rs1062033 Polymorphism in the CYP19A1 Gene	GC Genotype of rs1062033 Polymorphism in the CYP19A1 Gene	CC Genotype for the rs1062033
Arm/Group Description	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided into different genotypes of the rs1062033 polymorphism in the CYP19A1 gene Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. It is insoluble in water, freely soluble in alcohol, chloroform, dioxane, ether, and soluble in vegetable oils. The chemical name for testosterone cypionate is androst-4-en-3-one,17-(3-cyclopentyl-1oxopropoxy)-, (178)-. Its molecular formula is CvH400a, and the mole	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided into different genotypes of the rs1062033 polymorphism in the CYP19A1 gene	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided into different genotypes of the rs1062033 polymorphism in the CYP19A1 gene
Measure Participants	14	38	32
LUMBAR SPINE	4.72 (0.91)	2.85 (0.56)	3.74 (0.63)
FEMORAL NECK	-1.04 (1.31)	0.64 (0.81)	0.22 (0.96)
TOTAL HIP	0.33 (0.84)	0.70 (0.50)	0.64 (0.56)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene, GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene
	Comments	Analysis by intention to treat with the last value carry forward
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANOVA
	Comments

3. Secondary Outcome

Title	Percent Change in Bone Mineral Density According to Body Mass Index (BMI)
Description	Percent changes in bone mineral density from baseline
Time Frame	baseline to 18 months

Outcome Measure Data

Analysis Population Description

Analysis was by intention to treat with the last value carry forward. Thirty subjects in BMI group 1, 31 in BMI group 2 and 23 subjects in BMI groups 3 have complete dataset available for analysis. There were a total 84 patients who were able to provide data for this outcome at 18 months.

Arm/Group Title	BMI Group 1	BMI Group 2	BMI Group 3
Arm/Group Description	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided into different groups of BMI. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. It is insoluble in water, freely soluble in alcohol, chloroform, dioxane, ether, and soluble in vegetable oils. The chemical name for testosterone cypionate is androst-4-en-3-one,17-(3-cyclopentyl-1oxopropoxy)-, (178)-. Its molecular formula is CvH400a, and the mole	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided into different groups of BMI.	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided into different groups of BMI.
Measure Participants	30	31	23
lumbar spine	3.00 (0.97)	4.90 (0.96)	3.90 (1.24)
Total hip	0.14 (0.56)	1.74 (0.55)	-0.27 (0.64)
femoral neck	0.71 (0.83)	-0.33 (0.86)	0.16 (0.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene, GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene, AA Genotype for the rs700518 Polymorphism of the CYP19A1 Gene
	Comments	Analysis by intention to treat with the last value carry forward.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANOVA
	Comments

4. Secondary Outcome

Title	Percent Change in Prostate-specific Antigen (PSA) According to the rs700518 Polymorphism of the CYP19A1 Gene
Description	Percent change in PSA from baseline to 18 months
Time Frame	From baseline to 18 months

Outcome Measure Data

Analysis Population Description

More participants came for their 6-month blood test than for other outcomes e.g. BMD. Since our analysis was intention to treat with the last value carry forward, there were more patients with evaluable PSA data at 18 months, as some patients who had PSA but had no BMD testing etc. who dropped out of the study were also included in the analysis.

Arm/Group Title	GG Genotype for the rs700518 Polymor[Hism of the CYP19A1 Gene	GA Genotype of the rs700518 Polymorphism in CYP19A1 Gen	AA Genotype for the rs700518 Polymorphism of the CYP19A1 Gene
Arm/Group Description	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided into different genotypes for the rs700518 polymorphism of the CYP19A1 gene Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. It is insoluble in water, freely soluble in alcohol, chloroform, dioxane, ether, and soluble in vegetable oils. The chemical name for testosterone cypionate is androst-4-en-3-one,17-(3-cyclopentyl-1oxopropoxy)-, (178)-. Its molecular formula is CvH400a, and the mole	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided into different genotypes for the rs700518 polymorphism of the CYP19A1 gene	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided into different genotypes for the rs700518 polymorphism of the CYP19A1 gene
Measure Participants	17	46	26
Mean (Standard Deviation) [percent change]	105.78 (167.93)	58.52 (76.14)	44.44 (59.92)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene, GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene
	Comments	Analysis by intention to treat with the last value carry forward.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANOVA
	Comments

5. Secondary Outcome

Title	Percent Change in Prostate-specific Antigen (PSA) According to the rs1062033 Polymorphism of the CYP19A1 Gene
Description	Percent change in PSA from baseline at 18 months
Time Frame	from baseline to 18 months

Outcome Measure Data

Analysis Population Description

More participants came for their 6-month blood test than for other outcomes e.g. BMD. Since our analysis was intention to treat with the last value carry forward, there were more patients with evaluable PSA data at 18 months, as some patients who had PSA but had no BMD testing etc. who dropped out of the study were also included in the analysis.

Arm/Group Title	GG Genotype of the rs1062033 Polymorphism in the CYP19A1 Gene	GC Genotype of rs1062033 Polymorphism in the CYP19A1 Gene	CC Genotype for the rs1062033 Polymorphism in the CYP19A1 Gene
Arm/Group Description	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided into different genotypes of the rs1062033 polymorphism in the CYP19A1 gene Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. It is insoluble in water, freely soluble in alcohol, chloroform, dioxane, ether, and soluble in vegetable oils. The chemical name for testosterone cypionate is androst-4-en-3-one,17-(3-cyclopentyl-1oxopropoxy)-, (178)-. Its molecular formula is CvH400a, and the mole	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided into different genotypes of the rs1062033 polymorphism in the CYP19A1 gene	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided into different genotypes of the rs1062033 polymorphism in the CYP19A1 gene
Measure Participants	17	46	26
Mean (Standard Deviation) [precent change]	85.15 (23.84)	62.86 (15.74)	52.93 (17.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene, GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene
	Comments	Analysis by intention to treat with the last value carry forward.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANOVA
	Comments

6. Secondary Outcome

Title	Percent Change in Hematocrit According to the Genotype of the 700518 Polymorphism of the CYP19A1gene
Description	Percent change in hematocrit from baseline to 18 months
Time Frame	baseline to 18 months

Outcome Measure Data

Analysis Population Description

Analysis was by intention to treat with the last value carry forward. Those who had at least one follow-up from baseline were included in the analysis. The data of 85 subjects were available for analysis; 16 subjects in the GG, 43 in the GC and 26 subjects in the CC genotype.

Arm/Group Title	GG Genotype for the rs700518 Polymorphism of the CYP19A1 Gene	GA Genotype for the rs700518 Polymorphism of the CYP19A1 Gene	AA Genotype for the rs700518 Polymorphism of the
Arm/Group Description	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided according to the genotypes of rs700718 polymorphism of the CYP19A1 gene. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. It is insoluble in water, freely soluble in alcohol, chloroform, dioxane, ether, and soluble in vegetable oils. The chemical name for testosterone cypionate is androst-4-en-3-one,17-(3-cyclopentyl-1oxopropoxy)-, (178)-. Its molecular formula is CvH400a, and the mole	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided according to the genotypes of rs700718 polymorphism of the CYP19A1 gene.	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided according to the genotypes of rs700718 polymorphism of the CYP19A1 gene.
Measure Participants	16	43	26
Mean (Standard Deviation) [Percent change]	11.32 (2.21)	9.71 (1.35)	9.41 (1.73)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene, GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene
	Comments	Analysis by intention to treat with the last value carry forward.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANOVA
	Comments

7. Secondary Outcome

Title	Percent Change in Hematocrit According to re1062033 Polymorphism of the CYP19A1 Gene
Description	Percent change in hematocrit from baseline to 18 months
Time Frame	Baseline to 18 months

Outcome Measure Data

Analysis Population Description

Analysis was by intention to treat with the last value carry forward. Those who had at least one follow-up from baseline were included in the analysis. The data of 85 subjects were available for analysis; 15 subjects in the GG, 37 in the GC and 33 subjects in the CC genotype.

Arm/Group Title	GG Genotype of the rs1062033 Polymorphism in the CYP19A1 Gene	GC Genotype of rs1062033 Polymorphism in the CYP19A1 Gene	CC Genotype of rs1062033 Polymorphism in the CYP19A1 Gene
Arm/Group Description	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided into different genotypes of the rs1062033 polymorphism in the CYP19A1 gene Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. It is insoluble in water, freely soluble in alcohol, chloroform, dioxane, ether, and soluble in vegetable oils. The chemical name for testosterone cypionate is androst-4-en-3-one,17-(3-cyclopentyl-1oxopropoxy)-, (178)-. Its molecular formula is CvH400a, and the mole	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided into different genotypes of the rs1062033 polymorphism in the CYP19A1 gene	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided into different genotypes of the rs1062033 polymorphism in the CYP19A1 gene.
Measure Participants	15	37	33
Mean (Standard Deviation) [percent change]	11.56 (2.28)	9.67 (1.45)	9.46 (1.54)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene, GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene
	Comments	Analysis by intention to treat with the last value carry forward.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANOVA
	Comments

8. Secondary Outcome

Title	Percent Change in Aromatase Gene Activity From the Buffy Coat According to the 700518 Polymorphism of the CYP19A1 Gene
Description	Percent change in gene expression from baseline to 18 months
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

Gene expression studies were successful in 27 samples; 6 in the GG, 17 in the GA and 4 in the AA genotype.

Arm/Group Title	GG Genotype for the rs700518 Polymorphism in the cYP19A1 Gene	GA Genoypr for the rs700518 Polymorphism of the CYP19A1 Gene	AA Genotype for the rs700518 Polymorphism of the CYP19A1 Gene
Arm/Group Description
Measure Participants	6	17	4
Mean (Standard Deviation) [percent change]	25.0 (120.0)	65.25 (71.29)	113.33 (146.97)

9. Secondary Outcome

Title	Percent Change in Bone Turnover Markers According to the rs700518 Polymorphism of the CYP19A1 Gene
Description	Percent change in bone turnover from baseline to 18 months.
Time Frame	Baseline to 18 months

Outcome Measure Data

Analysis Population Description

Analysis was by intention to treat with the last value carry forward. Those who had at least one follow-up from baseline were included in the analysis. The data of 79 subjects were analyzed; 15 in the GG, 43 in the GA and 21 in the AA genotype.

Arm/Group Title	GG Genotype for RS 700518 of the CYP19A1 Gene	GA Genotype for the rs700518 Polymorphism of the CYP19A1 Gene	AA Genotype for the rs700518 Polymorphism of the CYP19A1 Gene
Arm/Group Description	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided into the different genotypes for the rs700518 polymorphism of the CYP19A1 gene. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. It is insoluble in water, freely soluble in alcohol, chloroform, dioxane, ether, and soluble in vegetable oils. The chemical name for testosterone cypionate is androst-4-en-3-one,17-(3-cyclopentyl-1oxopropoxy)-, (178)-. Its molecular formula is CvH400a, and the mole	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided into the different genotypes for the rs700518 polymorphism of the CYP19A1 gene.	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided into the different genotypes for the rs700518 polymorphism of the CYP19A1 gene.
Measure Participants	15	43	21
C-teloepetide	41.47 (16.33)	3.35 (9.64)	-9.75 (13.80)
Osteocalcin	12.40 (133.13)	-31.22 (148.00)	-7.27 (112.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene, GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene
	Comments	Analysis was by intention to treat with the last value carry forward. Those who had at least one follow-up from baseline and with acceptable assay coefficient of variability were included in the analysis. The data of 79 subjects were analyzed; 15 in the GG, 43 in the GA and 21 in the AA genotype.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANOVA
	Comments

10. Secondary Outcome

Title	Percent Change in Bone Turnover Markers According to the rs1062033 Polymorphism of the CYP19A1 Gene
Description	Percent change in bone turnover markers
Time Frame	Baseline to 18 months

Outcome Measure Data

Analysis Population Description

Analysis was by intention to treat with the last value carry forward. Those who had at least one follow-up from baseline were included in the analysis. The data of 79 subjects with acceptable assay coefficient of variability were available for analysis; 15 subjects in the GG, 37 in the GC and 27 in the CC genotype.

Arm/Group Title	GG Genotype for the rs1062033 Polymorphism of the CYP19A1 Gene	GC Genotype for the rs1062033 Polymorphism of the	GG Genotype for the rs1062033 Polymorphism in the CYP19A1 Gene
Arm/Group Description	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided according to the genotypes of rs1062033 polymorphism of the CYP19A1 gene. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. It is insoluble in water, freely soluble in alcohol, chloroform, dioxane, ether, and soluble in vegetable oils. The chemical name for testosterone cypionate is androst-4-en-3-one,17-(3-cyclopentyl-1oxopropoxy)-, (178)-. Its molecular formula is CvH400a, and the mole	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided according to the genotypes of 1062033 polymorphism of the CYP19A1 gene.	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided according to the genotypes of 1062033 polymorphism of the CYP19A1 gene.
Measure Participants	15	37	27
C-telopeptide	48.96 (98.42)	5.89 (48.82)	-14.49 (51.05)
Osteocalcin	33.59 (118.59)	-20.59 (128.37)	-26.96 (144.48)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene, GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene
	Comments	Analysis by intention to treat with the last value carry forward.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANOVA
	Comments

11. Secondary Outcome

Title	Percent Change in Bone Mineral Density According the Presence of Diabetes Mellitus
Description	Percent change in bone mineral density from baseline to 18 months
Time Frame	Baseline to 18 months

Outcome Measure Data

Analysis Population Description

Analysis was by intention to treat with the last value carry forward. Thirty-nine subjects with diabetes mellitus group and 45 without diabetes mellitus have complete dataset available for analysis.

Arm/Group Title	Subjects With Diabetes Mellitus	Subjects Without Diabetes Mellitus
Arm/Group Description	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided into those with and without diabetes mellitus. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. It is insoluble in water, freely soluble in alcohol, chloroform, dioxane, ether, and soluble in vegetable oils. The chemical name for testosterone cypionate is androst-4-en-3-one,17-(3-cyclopentyl-1oxopropoxy)-, (178)-. Its molecular formula is CvH400a, and the mole	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided into those with and without diabetes mellitus.
Measure Participants	39	45
LUMBAR SPINE	4.05 (0.60)	3.28 (0.51)
TOTAL HIP	1.81 (0.61)	0.53 (0.49)
FEMORAL NECK	1.63 (0.95)	-0.55 (0.79)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene, GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene
	Comments	Analysis by intention to treat with the last value carry forward.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANOVA
	Comments

12. Secondary Outcome

Title	Percent Change in Bone Turnover Markers According the Presence of Diabetes Mellitus
Description	Percent change in bone turnover markers from baseline to 18 months.
Time Frame	Baseline to 18 months

Outcome Measure Data

Analysis Population Description

Analysis was by intention to treat with the last value carry forward. Thirty-seven subjects with diabetes mellitus group and 41 without diabetes mellitus have complete dataset available for analysis.

Arm/Group Title	Subjects With Diabetes Mellitus	Subjects Without Diabetes Mellitus
Arm/Group Description	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided into those with and without diabetes mellitus. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. It is insoluble in water, freely soluble in alcohol, chloroform, dioxane, ether, and soluble in vegetable oils. The chemical name for testosterone cypionate is androst-4-en-3-one,17-(3-cyclopentyl-1oxopropoxy)-, (178)-. Its molecular formula is CvH400a, and the mole	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Subjects were divided into those with and without diabetes mellitus.
Measure Participants	37	41
C-telopeptide	73.55 (22.88)	2.05 (16.22)
Osteocalcin	20.54 (15.64)	-6.62 (10.54)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GG Genotype for RS 700518 Polymorphism of the CYP19A1 Gene, GA Genotype for the rs700518 Polymorphisms of the CYP19A1 Gene
	Comments	Analysis by intention to treat with the last value carry forward.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANOVA
	Comments

Adverse Events

Time Frame	18 months
Arm/Group Title	Arm 1: Testosterone Cypionate
Arm/Group Description	All patients who qualify for the study will receive testosterone cypionate Testosterone Cypionate: DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. It is insoluble in water, freely soluble in alcohol, chloroform, dioxane, ether, and soluble in vegetable oils. The chemical name for testosterone cypionate is androst-4-en-3-one,17-(3-cyclopentyl-1oxopropoxy)-, (178)-. Its molecular formula is CvH400a, and the mole
All Cause Mortality
	Arm 1: Testosterone Cypionate
	Affected / at Risk (%)	# Events
Total	0/105 (0%)
Serious Adverse Events
	Arm 1: Testosterone Cypionate
	Affected / at Risk (%)	# Events
Total	18/105 (17.1%)
Cardiac disorders
coronary stent	2/105 (1.9%)
atypical chest pain	1/105 (1%)
new-onset atrial fibrillation	1/105 (1%)
myocardial infarction	2/105 (1.9%)
Gastrointestinal disorders
appendicitis	1/105 (1%)
GI tract perforation	1/105 (1%)
Infections and infestations
abscess	1/105 (1%)
infection of an appendectomy wound	1/105 (1%)
Musculoskeletal and connective tissue disorders
knee arthroscopy	1/105 (1%)
knee replacement surgery	1/105 (1%)
Nervous system disorders
stroke	2/105 (1.9%)
Psychiatric disorders
pyschiatric ilness	4/105 (3.8%)
Other (Not Including Serious) Adverse Events
	Arm 1: Testosterone Cypionate
	Affected / at Risk (%)	# Events
Total	51/105 (48.6%)
Blood and lymphatic system disorders
high hematocrit	9/105 (8.6%)
hemochromatosis	1/105 (1%)
Cardiac disorders
Congestive heart failure	1/105 (1%)
Gastrointestinal disorders
appendicitis	1/105 (1%)
diverticulitis	2/105 (1.9%)
heartburn	1/105 (1%)
infected appendectomy wound	1/105 (1%)
General disorders
sleep apnea	1/105 (1%)
Hepatobiliary disorders
gallstones	1/105 (1%)
Infections and infestations
infected spider bite	1/105 (1%)
shingles	1/105 (1%)
cellulitis	1/105 (1%)
Injury, poisoning and procedural complications
back pain	1/105 (1%)
retinal injury	1/105 (1%)
Musculoskeletal and connective tissue disorders
ingrown toenail	1/105 (1%)
heel pain	1/105 (1%)
arthroplasty	3/105 (2.9%)
foot pain	1/105 (1%)
vertebral fracture	1/105 (1%)
osteoarthritis	3/105 (2.9%)
excision of bone spur	2/105 (1.9%)
knee replacement	1/105 (1%)
Nervous system disorders
headache	1/105 (1%)
Psychiatric disorders
mood swings	1/105 (1%)
irritability	1/105 (1%)
depression	1/105 (1%)
Renal and urinary disorders
prostate enlargement	1/105 (1%)
Reproductive system and breast disorders
priapism	1/105 (1%)
mastitis	1/105 (1%)
Respiratory, thoracic and mediastinal disorders
upper respiratory infection	1/105 (1%)
dyspnea	1/105 (1%)
lung carcinoma	1/105 (1%)
Skin and subcutaneous tissue disorders
alopecia	1/105 (1%)
acne	1/105 (1%)
laceration	3/105 (2.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.