NaF Positron Emission Tomography/Computed Tomography (PET/CT)Imaging to Assess Treatment Responsiveness to TAK-700 in Patients With Castrate Resistant Prostate Cancer (CRPC) With Bone Metastasis

• Sponsor: University of Wisconsin, Madison (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01816048
• Collaborator: Millennium Pharmaceuticals, Inc. (Industry)
• Enrollment: 8
• Location: 1
• Arm: 1
• Duration (Months): 42.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to assess whether NaF PET/CT scans can be used to evaluate treatment response in bone metastases in subjects with prostate cancer treated with the investigational drug, TAK-700.

Condition or Disease	Intervention/Treatment	Phase
Prostatic Neoplasms; Prostate Cancer	Drug: TAK-700; Radiation: Fluorine F 18 Sodium Fluoride; Procedure: Positron Emission Tomography; Procedure: Computed Tomography	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pharmacodynamic Study Using NaF PET/CT Imaging to Assess Treatment Responsiveness to TAK-700 in Patients With Metastatic Castrate Resistant Prostate Cancer to Bone
• Study Start Date: May 1, 2013
• Actual Primary Completion Date: Dec 1, 2015
• Actual Study Completion Date: Nov 1, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: TAK-700 TAK-700 will be administered at 300 mg orally (PO)twice daily (BID) continuously on 28-day treatment cycles. The most common way of assessing bone metastasis is planar bone scintigraphy or single photon emission computed tomography (SPECT), though both lack high spatial resolution and thus make small metastases detection inaccurate. Positron emission tomography (PET) is a successful imaging modality with a higher resolution than SPECT, but has not been widely adopted in bone imaging. One of the most promising PET imaging agents for detection of bone metastasis is 18F-Sodium Fluoride (Fluorine F 18 Sodium Fluoride, or NaF). NaF uptake is characterized by high and rapid bone uptake accompanied by very rapid blood clearance, which results in a high bone-to-background ration in a short time.

Drug: TAK-700; TAK-700 will be administered at 300mg twice per day on 28-day continuous cycles; Other Names: orteronel ; Radiation: Fluorine F 18 Sodium Fluoride; Undergo NaF F18 PET/CT scan; Other Names: 18 F-NaF F-18 NaF ; Procedure: Positron Emission Tomography; Undergo 18F NaF PET/CT scan; Other Names: PET ; Procedure: Computed Tomography; Undergo 18F NaF PET/CT scan; Other Names: CT CAT Scan

Outcome Measures

Primary Outcome Measures

1. Number of Participants With a Change in Maximum NaF PET/CT Standardized Uptake Values [Baseline and 3 months]

   To measure changes in NaF PET/CT standardized uptake values (SUVmax) from prior to dosing with Tak-700 to12 weeks after starting treatment with TAK-700. Value at three months minus value at baseline.

2. Number of Participants With Change in Prostate Specific Antigen (PSA) Response Rate [Baseline and 3 months]

   Measure prostate specific antigen (PSA) response rate in patients treated with TAK700, as measured by a decline in the PSA level from baseline to the month 3 assessment according to the Prostate Cancer Clinical Trials Working Group (PCWG2), at least a 50% decrease from baseline. Percent increase or decrease from month three compared to baseline.

3. Number of Participants With a Change in Total NaF PET/CT Standardized Uptake Values [Baseline and 3 months]

   To measure changes in NaF PET/CT standardized uptake values (SUV total) from prior to dosing with Tak-700 to12 weeks after starting treatment with TAK-700. Percent change from three months to baseline; value at three months minus value at baseline.

Secondary Outcome Measures

1. Number of Subjects Who Experience Adverse Events While on Treatment With TAK 700 [Up to 12 months]

   The number of subjects experiencing adverse events per CTCAE 4.0 while on treatment.

2. Number of Patients With a Measurable Change in PSA Kinetics With TAK700 From Baseline to Off Treatment [Up to 14 months]

   Stable: no change in PSA kinetics Decrease: less than baseline Increase: greater than baseline PSA data was gathered at baseline and off treatment.

3. Number of Participants With Changes in NaF PET/CT Results in Response to TAK700 [At baseline and 12 weeks]

   This is an exploratory endpoint as we are planning to identify other new parameters during the PET/CT scanning that may be more predictive of response (such as SUV volume, or dynamic changes during the scanning period). Changes in results at week 12 compared to baseline. Value at 12 weeks minus value at baseline.

4. Compare Changes on NaF PET/CT After Treatment With TAK700 With Standard Clinical Outcomes Including PSA Doubling Time, Response Evaluation Criteria in Solid Tumors (RECIST), and Radiographic Progression Free Survival. [Approximately 24 months]

5. Number of Participants With a Change in the Number of Circulating Tumor Cells Using One or More Methods (Epispot) [At baseline and 12 weeks]

   Baseline compared to 12 weeks. Value at three months minus value at baseline.

6. Number of Participants With Change in the Number of Circulating Tumor Cells Using the Cell Search System (Veridex, LLC) Obtained Prior to Beginning Treatment With TAK 700, After Completing One Cycle and After Completing 3 Cycles [At baseline, one month, three months]

   Change from baseline to one month and three month.

7. PSA Response Rate and Circulating Tumor Cell Counts of Subjects Receiving TAK700 to NaF PET/CT Imaging Results [Baseline, one month, 2 months, 3 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male patients 18 years or older

• Voluntary written consent

• Histologically proven adenocarcinoma of the prostate

• Evidence of radiographic bone metastases

• May have received prior chemotherapy for metastatic disease, but prior chemotherapy is not a requirement for eligibility

• Eastern Cooperative Oncology Group performance status 0-2

• Serum testosterone level is less than or equal to 50 ng/dL

• Has undergone orchiectomy or plan to continue receiving gonadotropin releasing hormone (GnRH) analogue therapy

• Adequate organ function as measured by screening laboratory values specified in the protocol

• Must agree to use appropriate contraceptives prior to study procedures, during duration of study participation and for 4 months after last dose of TAK 700

• Must be able to lie flat for greater than or equal to 30 minutes during PET/CT imaging

• Screening calculated ejection fraction of greater than or equal to 50% by multigated radionuclide angiography (MUGA) scan or Echocardiogram

Exclusion Criteria:

• Received Strontium-89, Samarium-153, or other radioisotope within 3 months of registration

• history of allergic reactions attributed to compounds similar to sodium fluoride F-18 (NaF)

• history of seizure disorder

• Known history of brain metastases

• Concurrent treatment with any herbal products within 7 days of study entry

• Received radiotherapy less than or equal to 4 weeks prior to registration

• Known hypersensitivity to TAK-700 or related compounds

• Prior therapy for treatment of metastatic castrate resistant prostate cancer with any androgen biosynthesis inhibitor or androgen signaling pathway inhibitor such as: enzalutamide (MDV-3100), abiraterone, ketoconazole, or aminoglutethimide

• Current bladder neck outlet obstruction

• Current spinal cord compression

• Current bilateral hydronephrosis

• History of adrenal insufficiency

• History of myocardial infarction, unstable symptomatic ischemic heart disease, ongoing arrhythmias (over grade 2), thromboembolic events, or any other cardiac condition within 6 months prior to first dose of study drug.

• Uncontrolled high blood pressure

• Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C

• Major surgery less than or equal to 4 weeks before the first dose of study drug

• Serious infection less than or equal to 2 weeks before the first dose of study drug

• Known gastrointestinal (GI) disease or GI procedure that could interfere with oral absorption or tolerance of TAK-700, including difficulty swallowing capsules

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• University of Wisconsin, Madison
• Millennium Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Justine Y Bruce, MD, University of Wisconsin, Madison

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Wisconsin Carbone Cancer Center

Publications

None provided.

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT01816048
• Other Study ID Numbers: CO12810; 2012-1107; NCI-2013-01081; A534260; SMPH\MEDICINE\HEM-ONC
• First Posted: Mar 21, 2013
• Last Update Posted: Dec 9, 2019
• Last Verified: Dec 1, 2017

• Keywords provided by University of Wisconsin, Madison: prostate, prostate cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Listerine; Fluorides; Sodium Fluoride

Study Results

Participant Flow

Arm/Group Title	TAK-700
Arm/Group Description	TAK-700 was administered at 300 mg orally (PO)twice daily (BID) continuously on 28-day treatment cycles. TAK-700: TAK-700 will be administered at 300mg twice per day on 28-day continuous cycles Fluorine F 18 Sodium Fluoride: Undergo NaF F18 PET/CT scan Positron Emission Tomography: Undergo 18F NaF PET/CT scan Computed Tomography: Undergo 18F NaF PET/CT scan
Period Title: Overall Study
STARTED	8
COMPLETED	2
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	TAK-700
Arm/Group Description	TAK-700 was administered at 300 mg orally (PO)twice daily (BID) continuously on 28-day treatment cycles. TAK-700: TAK-700 will be administered at 300mg twice per day on 28-day continuous cycles Fluorine F 18 Sodium Fluoride: Undergo NaF F18 PET/CT scan Positron Emission Tomography: Undergo 18F NaF PET/CT scan Computed Tomography: Undergo 18F NaF PET/CT scan
Overall Participants	8
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 25%
>=65 years	6 75%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	8 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	8 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	8 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	8 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With a Change in Maximum NaF PET/CT Standardized Uptake Values
Description	To measure changes in NaF PET/CT standardized uptake values (SUVmax) from prior to dosing with Tak-700 to12 weeks after starting treatment with TAK-700. Value at three months minus value at baseline.
Time Frame	Baseline and 3 months

Outcome Measure Data

Analysis Population Description

The study closed early so only 8 of 20 planned were enrolled and of the 8, only 4 completed the week 12 scan.

Arm/Group Title	TAK-700
Arm/Group Description	TAK-700 was administered at 300 mg orally (PO)twice daily (BID) continuously on 28-day treatment cycles. TAK-700: TAK-700 will be administered at 300mg twice per day on 28-day continuous cycles Fluorine F 18 Sodium Fluoride: Undergo NaF F18 PET/CT scan Positron Emission Tomography: Undergo 18F NaF PET/CT scan Computed Tomography: Undergo 18F NaF PET/CT scan
Measure Participants	4
SUVmax decrease	3 37.5%
SUVmax increase	1 12.5%

2. Primary Outcome

Title	Number of Participants With Change in Prostate Specific Antigen (PSA) Response Rate
Description	Measure prostate specific antigen (PSA) response rate in patients treated with TAK700, as measured by a decline in the PSA level from baseline to the month 3 assessment according to the Prostate Cancer Clinical Trials Working Group (PCWG2), at least a 50% decrease from baseline. Percent increase or decrease from month three compared to baseline.
Time Frame	Baseline and 3 months

Outcome Measure Data

Analysis Population Description

Study closed early and only 8 of planned 20 enrolled. Four subjects came off study prior to the three month time point.

Arm/Group Title	TAK-700
Arm/Group Description	TAK-700 was administered at 300 mg orally (PO)twice daily (BID) continuously on 28-day treatment cycles. TAK-700: TAK-700 will be administered at 300mg twice per day on 28-day continuous cycles Fluorine F 18 Sodium Fluoride: Undergo NaF F18 PET/CT scan Positron Emission Tomography: Undergo 18F NaF PET/CT scan Computed Tomography: Undergo 18F NaF PET/CT scan
Measure Participants	4
PSA decline >= 50%	3 37.5%
PSA decline =< 50%	1 12.5%

3. Secondary Outcome

Title	Number of Subjects Who Experience Adverse Events While on Treatment With TAK 700
Description	The number of subjects experiencing adverse events per CTCAE 4.0 while on treatment.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TAK-700
Arm/Group Description	TAK-700 will be administered at 300 mg orally (PO)twice daily (BID) continuously on 28-day treatment cycles. TAK-700: TAK-700 will be administered at 300mg twice per day on 28-day continuous cycles Fluorine F 18 Sodium Fluoride: Undergo NaF F18 PET/CT scan at screen, week 4-8 and week 12
Measure Participants	8
Number [participants]	8 100%

4. Secondary Outcome

Title	Number of Patients With a Measurable Change in PSA Kinetics With TAK700 From Baseline to Off Treatment
Description	Stable: no change in PSA kinetics Decrease: less than baseline Increase: greater than baseline PSA data was gathered at baseline and off treatment.
Time Frame	Up to 14 months

Outcome Measure Data

Analysis Population Description

Due to study closing early only 8 of planned 20 patients enrolled.

Arm/Group Title	TAK-700
Arm/Group Description	TAK-700 will be administered at 300 mg orally (PO)twice daily (BID) continuously on 28-day treatment cycles. TAK-700: TAK-700 will be administered at 300mg twice per day on 28-day continuous cycles Fluorine F 18 Sodium Fluoride: Undergo NaF F18 PET/CT scan at screen, week 4-8 and week 12
Measure Participants	8
Stable	1 12.5%
Decrease in PSA	3 37.5%
Increase in PSA	4 50%

5. Secondary Outcome

Title	Number of Participants With Changes in NaF PET/CT Results in Response to TAK700
Description	This is an exploratory endpoint as we are planning to identify other new parameters during the PET/CT scanning that may be more predictive of response (such as SUV volume, or dynamic changes during the scanning period). Changes in results at week 12 compared to baseline. Value at 12 weeks minus value at baseline.
Time Frame	At baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Due to study closing early only 8 of planned 20 patients enrolled and only 4 of the 8 subjects enrolled completed the week 12 scan.

Arm/Group Title	TAK-700
Arm/Group Description	TAK-700 was administered at 300 mg orally (PO)twice daily (BID) continuously on 28-day treatment cycles. TAK-700: TAK-700 will be administered at 300mg twice per day on 28-day continuous cycles Fluorine F 18 Sodium Fluoride: Undergo NaF F18 PET/CT scan Positron Emission Tomography: Undergo 18F NaF PET/CT scan Computed Tomography: Undergo 18F NaF PET/CT scan
Measure Participants	4
Increase in SUV total	1 12.5%
No change	1 12.5%
Decrease in SUV total	2 25%

6. Secondary Outcome

Title	Compare Changes on NaF PET/CT After Treatment With TAK700 With Standard Clinical Outcomes Including PSA Doubling Time, Response Evaluation Criteria in Solid Tumors (RECIST), and Radiographic Progression Free Survival.
Time Frame	Approximately 24 months

Outcome Measure Data

Analysis Population Description

Due to study closing early, only 8 of planned 20 patients enrolled. Data for this endpoint was not obtained.

Arm/Group Title	TAK-700
Arm/Group Description	TAK-700 will be administered at 300 mg orally (PO)twice daily (BID) continuously on 28-day treatment cycles. TAK-700: TAK-700 will be administered at 300mg twice per day on 28-day continuous cycles Fluorine F 18 Sodium Fluoride: Undergo NaF F18 PET/CT scan at screen, week 4-8 and week 12
Measure Participants	0

7. Secondary Outcome

Title	Number of Participants With a Change in the Number of Circulating Tumor Cells Using One or More Methods (Epispot)
Description	Baseline compared to 12 weeks. Value at three months minus value at baseline.
Time Frame	At baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Due to study closing early only 8 of 12 patients enrolled, and only 5 subjects obtained a week 12 CTC test.

Arm/Group Title	TAK-700
Arm/Group Description	TAK-700 will be administered at 300 mg orally (PO)twice daily (BID) continuously on 28-day treatment cycles. TAK-700: TAK-700 will be administered at 300mg twice per day on 28-day continuous cycles Fluorine F 18 Sodium Fluoride: Undergo NaF F18 PET/CT scan at screen, week 4-8 and week 12
Measure Participants	5
Increase in circulating tumors	2 25%
Decrease in circulating tumors	3 37.5%

8. Secondary Outcome

Title	Number of Participants With Change in the Number of Circulating Tumor Cells Using the Cell Search System (Veridex, LLC) Obtained Prior to Beginning Treatment With TAK 700, After Completing One Cycle and After Completing 3 Cycles
Description	Change from baseline to one month and three month.
Time Frame	At baseline, one month, three months

Outcome Measure Data

Analysis Population Description

Due to study closing early only 8 of planned 20 enrolled. All subjects completed one month of treatment; only 4 subjects completed the week 12 scan.

Arm/Group Title	TAK-700
Arm/Group Description	TAK-700 will be administered at 300 mg orally (PO)twice daily (BID) continuously on 28-day treatment cycles. TAK-700: TAK-700 will be administered at 300mg twice per day on 28-day continuous cycles Fluorine F 18 Sodium Fluoride: Undergo NaF F18 PET/CT scan at screen, week 4-8 and week 12
Measure Participants	8
Increase in circulating tumors	2 25%
Decrease in circulating tumors	5 62.5%
No change	1 12.5%
Increase in circulating tumors	1 12.5%
Decrease in circulating tumors	1 12.5%
No change	2 25%

9. Secondary Outcome

Title	PSA Response Rate and Circulating Tumor Cell Counts of Subjects Receiving TAK700 to NaF PET/CT Imaging Results
Time Frame	Baseline, one month, 2 months, 3 months

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome measure.

Arm/Group Title	TAK-700
Arm/Group Description	TAK-700 will be administered at 300 mg orally (PO)twice daily (BID) continuously on 28-day treatment cycles. TAK-700: TAK-700 will be administered at 300mg twice per day on 28-day continuous cycles Fluorine F 18 Sodium Fluoride: Undergo NaF F18 PET/CT scan at screen, week 4-8 and week 12
Measure Participants	0

10. Primary Outcome

Title	Number of Participants With a Change in Total NaF PET/CT Standardized Uptake Values
Description	To measure changes in NaF PET/CT standardized uptake values (SUV total) from prior to dosing with Tak-700 to12 weeks after starting treatment with TAK-700. Percent change from three months to baseline; value at three months minus value at baseline.
Time Frame	Baseline and 3 months

Outcome Measure Data

Analysis Population Description

The study closed early so only 8 of 20 planned were enrolled and of the 8, only 4 completed the week 12 scan.

Arm/Group Title	TAK-700
Arm/Group Description	TAK-700 was administered at 300 mg orally (PO)twice daily (BID) continuously on 28-day treatment cycles. TAK-700: TAK-700 will be administered at 300mg twice per day on 28-day continuous cycles Fluorine F 18 Sodium Fluoride: Undergo NaF F18 PET/CT scan Positron Emission Tomography: Undergo 18F NaF PET/CT scan Computed Tomography: Undergo 18F NaF PET/CT scan
Measure Participants	4
SUV total increase	1 12.5%
SUV total decrease	2 25%
SUV total no change	1 12.5%

Adverse Events

Time Frame	1 year, 11 months
Adverse Event Reporting Description	All patients were followed for adverse events for at least 30 days after the last dose of TAK-700, or before the initiation of another systemic antineoplastic therapy, whichever came first. Adverse events were assessed at all study visits and follow ups.
Arm/Group Title	TAK-700
Arm/Group Description	TAK-700 was administered at 300 mg orally (PO)twice daily (BID) continuously on 28-day treatment cycles. TAK-700: TAK-700 will be administered at 300mg twice per day on 28-day continuous cycles Fluorine F 18 Sodium Fluoride: Undergo NaF F18 PET/CT scan Positron Emission Tomography: Undergo 18F NaF PET/CT scan Computed Tomography: Undergo 18F NaF PET/CT scan
All Cause Mortality
	TAK-700
	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)
Serious Adverse Events
	TAK-700
	Affected / at Risk (%)	# Events
Total	4/8 (50%)
Cardiac disorders
Left ventricular systolic dysfunction	1/8 (12.5%)	1
Gastrointestinal disorders
Dehydration	1/8 (12.5%)	1
Diarrhea	1/8 (12.5%)	1
General disorders
sudden death	1/8 (12.5%)	1
Infections and infestations
Urinary tract infection	1/8 (12.5%)	1
Metabolism and nutrition disorders
Hypokalemia	1/8 (12.5%)	1
Nervous system disorders
Nerve impingement	1/8 (12.5%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/8 (12.5%)	1
Other (Not Including Serious) Adverse Events
	TAK-700
	Affected / at Risk (%)	# Events
Total	8/8 (100%)
Gastrointestinal disorders
Abdominal pain	2/8 (25%)	2
Anorexia	5/8 (62.5%)	6
Bloating	1/8 (12.5%)	1
Constipation	2/8 (25%)	3
Diarrhea	2/8 (25%)	4
Dry mouth	1/8 (12.5%)	1
Nausea	7/8 (87.5%)	14
Pancreatitis	1/8 (12.5%)	1
Stomach pain	1/8 (12.5%)	1
Vomiting	2/8 (25%)	2
General disorders
Edema limbs	1/8 (12.5%)	1
Fatigue	4/8 (50%)	4
Fever	1/8 (12.5%)	1
Pain	3/8 (37.5%)	8
Immune system disorders
Allergic rhinitis	1/8 (12.5%)	1
Infections and infestations
Rhinitis infective	1/8 (12.5%)	1
Sinusitis	1/8 (12.5%)	1
Injury, poisoning and procedural complications
Injury, arm	1/8 (12.5%)	1
Investigations
Ejection fraction decreased	1/8 (12.5%)	1
Weight loss	3/8 (37.5%)	3
Metabolism and nutrition disorders
Dehydration	2/8 (25%)	3
Hypokalemia	4/8 (50%)	7
Hypomagnesemia	1/8 (12.5%)	1
Musculoskeletal and connective tissue disorders
Back pain	4/8 (50%)	6
Generalized muscle weakness	2/8 (25%)	2
Muscle weakness lower limb	1/8 (12.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
neoplasms benigh, malignant and unspecified	1/8 (12.5%)	1
Nervous system disorders
Headache	4/8 (50%)	6
Peripheral sensory neuropathy	1/8 (12.5%)	1
nerve impingement	1/8 (12.5%)	1
Psychiatric disorders
Anxiety	1/8 (12.5%)	1
Depression	1/8 (12.5%)	1
Insomnia	3/8 (37.5%)	3
Renal and urinary disorders
Disuria	2/8 (25%)	2
Renal calculi	1/8 (12.5%)	1
Urinary frequency	1/8 (12.5%)	1
Urinary incontinence	1/8 (12.5%)	1
Urinary tract infection	1/8 (12.5%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/8 (12.5%)	1
Hoarseness	1/8 (12.5%)	1
Nasal congestion	1/8 (12.5%)	1
Productive cough	2/8 (25%)	2
Skin and subcutaneous tissue disorders
Dry skin	2/8 (25%)	2
Vascular disorders
Hot flashes	1/8 (12.5%)	1
Hypertension	3/8 (37.5%)	3

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.