Apalutamide in Treating Patients With Prostate Cancer Who Are in Active Surveillance

• Sponsor: University of Washington (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02721979
• Collaborator: Janssen Scientific Affairs, LLC (Industry), National Cancer Institute (NCI) (NIH)
• Enrollment: 24
• Location: 1
• Arm: 1
• Actual Duration (Months): 48.9
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This phase II trial studies how well apalutamide works in treating patients with prostate cancer who are in active surveillance. Testosterone can cause the growth of prostate cancer cells. Hormone therapy using androgen receptor antagonist apalutamide may fight prostate cancer by blocking the use of testosterone by the tumor cells.

Condition or Disease	Intervention/Treatment	Phase
Prostate Adenocarcinoma	Drug: Apalutamide; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Other: Questionnaire Administration	Phase 2

Detailed Description

OUTLINE:

Patients receive apalutamide orally (PO) once daily (QD) for 90 days in the absence of disease progression or unacceptable toxicity.

After completion of the study treatment, patients are followed up at 180, 365, 545, and 730 days; and at years 3, 4 and 5 by medical record review.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of Apalutamide in Active Surveillance Patients
• Actual Study Start Date: Nov 2, 2017
• Actual Primary Completion Date: Feb 12, 2020
• Actual Study Completion Date: Nov 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (apalutamide) Patients receive apalutamide PO QD for 90 days in the absence of disease progression or unacceptable toxicity.	Drug: Apalutamide; Given PO; Other Names: ARN 509 ARN-509 ARN509 JNJ 56021927 JNJ-56021927 ; Other: Laboratory Biomarker Analysis; Correlative studies; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment ; Other: Questionnaire Administration; Ancillary studies

Outcome Measures

Primary Outcome Measures

1. Negative (i.e. no Residual Carcinoma) Site Directed and Systematic Prostate Biopsy Rate [At 90 days]

   Negative rate will be presented as the percent of subjects with a negative repeat biopsy, and will be calculated as: (number of patients with a negative biopsy following 90-days of apalutamide) / (total number of patients enrolled on the study) x 100. A 1-sample chi-square test will be used to compare the proportion with a negative repeat biopsy to the null hypothesis value of 20% (above). The 95% confidence interval will be computed.

Secondary Outcome Measures

1. Percentage of Patients Exiting Active Surveillance Due to Pathologic Reclassification [At 2 years]

   The percentage of patients that exit active surveillance due to pathologic reclassification (e.g. increasing tumor volume or gleason score) will be computed along with its 95% confidence interval.

2. Percentage of Patients Exiting Active Surveillance for Any Reason [At 2 years]

   Percentage of patients exiting active surveillance for any reason will be computed along with its 95% confidence interval.

3. Percent of Men Undergoing of Local Treatment [At 2 years]

   Computed along with its 95% confidence interval.

4. Local Treatment Free Survival [Up to 730 days]

   Kaplan-Meier methods and 95% confidence interval will be estimated using Greenwood's formula.

5. Prostate-specific Antigen Progression Rate [At 2 years]

   Prostate-specific antigen progression rate will be defined per Prostate Cancer Working Group 2 criteria (i.e. confirmed rising prostate-specific antigen >= 2 ng/mL at least one week apart) and will be computed along with 95% confidence interval.

6. Prostate-specific Antigen Progression Free Survival as Defined by the Prostate Cancer Working Group 2 Criteria [At 2 years]

   Prostate-specific antigen progression free survival will be estimated using Kaplan-Meier methods and 95% confidence interval will be estimated using Greenwood's formula.

7. Change in Radiographic Disappearance of Magnetic Resonance Imaging Detectable Prostate Cancer [Baseline to up to 90 days]

   This calculates the percentage of participants with radiographic disappearance of magnetic resonance imaging detectable prostate cancer. This is only in patients with a baseline nodule that is Prostate Imaging Reporting and Data System 3 or more and > 5 mm.

8. Incidence of Adverse Events [Up to 730 days]

   As assessed by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03.

9. Severity of Adverse Events [Up to 730 days]

   As assessed by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03.

10. Change in Quality of Life: FACT-P Assessment [Baseline to up to 730 days]

    As assessed using the Functional Assessment of Cancer Therapy-Prostate surveys. Functional Assessment of Cancer Therapy-Prostate is a validated quality of life survey specific for patients with prostate cancer.

11. Change in Quality of Life: SF-36 Assessment [Baseline to up to 730 days]

    As assessed using the Short Form-36 survey. Short Form-36 is a validated quality of life survey. This is a generic survey to assess an individual's overall well-being, and is not specific to one disease.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have signed an informed consent document

• Be willing/able to adhere to the prohibitions and restrictions specified in this protocol

• Written authorization for use and release of health and research study information has been obtained

• Life expectancy >= 10 years (as determined by the treating physician)

• Eastern Cooperative Oncology Group (ECOG) performance status =< 1

• Histologically confirmed adenocarcinoma of the prostate as documented by a minimum 12 core prostate biopsy completed within 1-year of enrollment (note: most recent prostate biopsy must have demonstrated prostatic adenocarcinoma)

• Favorable risk prostate cancer as defined by:

• Very low-risk:

• Clinical stage T1c disease

• PSA density (PSAD) < 0.15 ng/mL

• Gleason score 6

• =< 2 core biopsies with =< 50% involvement of any biopsy core with cancer, or unilateral disease =< 2 core biopsies with any percentage involvement OR

• Low risk:

• Clinical stage =< T2a

• PSA < 15 ng/mL

• Gleason score 6 OR

• Low-intermediate risk:

• Clinical stage T1c

• PSA < 15 ng/ml

• Gleason 3+4 present in =< 50% of one core/site as detected by systematic biopsy or MRI/transrectal ultrasound (TRUS) fusion guided biopsy

• Gleason 6 disease in all other cores / sites

• Willing and qualified for active surveillance at Johns Hopkins or the University of Washington

• Serum testosterone >= 150 ng/dL

• Able to swallow the study drugs whole as a tablet

• Hemoglobin >= 9.0 g/dL, (at screening), independent of transfusion and/or growth factors within 3 months prior to registration

• Platelet count >= 100,000 x 10^9/uL (at screening) independent of transfusion and/or growth factors within 3 months prior to registration

• Serum albumin >= 3.0 g/dL (at screening)

• Glomerular filtration rate (GFR) >= 45 mL/min (at screening)

• Serum potassium >= 3.5 mmol/L (at screening)

• Serum total bilirubin =< 1.5 x upper limit of normal (ULN) (at screening) (note: in subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is =< 1.5 x ULN, subject may be eligible)

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 × ULN (at screening)

• Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry

• Agrees to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug; must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug

Exclusion Criteria:

• Prior local therapy to treat prostate cancer (e.g. radical prostatectomy, radiation therapy, brachytherapy)

• Prior use of ARN-509 (apalutamide)

• Have known allergies, hypersensitivity, or intolerance to ARN-509 (apalutamide) or its excipients

• Prior or ongoing systemic therapy for prostate cancer including, but not limited to:

• Hormonal therapy (e.g. leuprolide, goserelin, triptorelin)

• Cytochrome P450 (CYP)-17 inhibitors (e.g. abiraterone, ketoconazole)

• Antiandrogens (e.g. bicalutamide, nilutamide)

• Second generation antiandrogens (e.g. enzalutamide)

• Immunotherapy (e.g. sipuleucel-T, ipilimumab)

• Chemotherapy (e.g. docetaxel, cabazitaxel)

• Have any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements

• History of any of the following:

• Seizure or known condition that may pre-dispose to seizure (including but not limited to prior stroke, transient ischemic attack, loss of consciousness within 1 year prior to registration, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)

• Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to registration

• Any condition that in the opinion of the investigator, would preclude participation in this study

• Current evidence of any of the following:

• Uncontrolled hypertension

• Gastrointestinal disorder affecting absorption

• Active infection (e.g. human immunodeficiency virus [HIV] or viral hepatitis) or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated

• Any condition that in the opinion of the investigator, would preclude participation in this study

• The use of drugs known to lower the seizure threshold, including: atypical antipsychotics (e.g. clozapine, olanzapine, risperidone, ziprasidone), bupropion, lithium, meperidine, pethidine, phenothiazine antipsychotics (e.g. chlorpromazine, mesoridazine, thioridazine), and tricyclic antidepressants (e.g. amitriptyline, desipramine, doxepin, imipramine, maprotiline, mirtazapine)

• The use of strong CYP3A4 inhibitors, including: itraconazole, clarithromycin, erythromycin, diltiazem, verapamil, delavirdine, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit juice (or grapefruits)

• Note: If a patient is on a strong CYP3A4 inhibitor, they can be reconsidered for enrollment if they can safely stop said medication; a two week or 5 half-lives, whichever is longer, washout will be required prior to enrolling on study; subject may not resume medication while receiving apalutamide

• Strong CYP3A4 inducers, including: phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, efavirenz, tipranavir, St. John's wort

**Note: If a patient is on a strong CYP3A4 inhibitor, they can be reconsidered for enrollment if they can safely stop said medication; a two week or 5 half-lives, whichever is longer, washout will be required prior to enrolling on study; subject may not resume medication while receiving apalutamide

• Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• University of Washington
• Janssen Scientific Affairs, LLC
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Michael Schweizer, Fred Hutch/University of Washington Cancer Consortium

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 26, 2020
• Informed Consent Form - May 30, 2019

More Information

Publications

None provided.

• Responsible Party: Michael Schweizer, Assistant Professor, Division of Medical Oncology, University of Washington
• ClinicalTrials.gov Identifier: NCT02721979
• Other Study ID Numbers: 9582; NCI-2016-00221; 9582; P30CA015704; RG1716037
• First Posted: Mar 29, 2016
• Last Update Posted: Jan 12, 2022
• Last Verified: Dec 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Adenocarcinoma

Study Results

Participant Flow

Recruitment Details	The screening study procedures are conducted within 30 days prior to enrollment. The only exception to this would be the surveillance prostate biopsy.
Pre-assignment Detail	24 subjects signed consent for this study, but only 23 were eligible to enter into the treatment phase.

Arm/Group Title	Apalutamide
Arm/Group Description	Day 1 until Day 90. Patients receive apalutamide PO QD for 90 days in the absence of disease progression or unacceptable toxicity. Apalutamide: Given PO Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies
Period Title: Overall Study
STARTED	23
COMPLETED	22
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Treatment (Apalutamide)
Arm/Group Description	Patients receive apalutamide PO QD for 90 days in the absence of disease progression or unacceptable toxicity. Apalutamide: Given PO Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies
Overall Participants	24
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	10 41.7%
>=65 years	14 58.3%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	24 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	24 100%
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	1 4.2%
White	23 95.8%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	24 100%
Patients with very low risk disease at baseline (Count of Participants)
Count of Participants [Participants]	9 37.5%

Outcome Measures

1. Primary Outcome

Title	Negative (i.e. no Residual Carcinoma) Site Directed and Systematic Prostate Biopsy Rate
Description	Negative rate will be presented as the percent of subjects with a negative repeat biopsy, and will be calculated as: (number of patients with a negative biopsy following 90-days of apalutamide) / (total number of patients enrolled on the study) x 100. A 1-sample chi-square test will be used to compare the proportion with a negative repeat biopsy to the null hypothesis value of 20% (above). The 95% confidence interval will be computed.
Time Frame	At 90 days

Outcome Measure Data

Analysis Population Description

These are patients that had 90 days of treatment and had post-treatment biopsies.

Arm/Group Title	Apalutamide
Arm/Group Description	Day 1 until Day 90. Patients receive apalutamide PO QD for 90 days in the absence of disease progression or unacceptable toxicity. Apalutamide: Given PO Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies
Measure Participants	22
Number (95% Confidence Interval) [percentage of subjects]	59

2. Secondary Outcome

Title	Percentage of Patients Exiting Active Surveillance Due to Pathologic Reclassification
Description	The percentage of patients that exit active surveillance due to pathologic reclassification (e.g. increasing tumor volume or gleason score) will be computed along with its 95% confidence interval.
Time Frame	At 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Percentage of Patients Exiting Active Surveillance for Any Reason
Description	Percentage of patients exiting active surveillance for any reason will be computed along with its 95% confidence interval.
Time Frame	At 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Percent of Men Undergoing of Local Treatment
Description	Computed along with its 95% confidence interval.
Time Frame	At 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Local Treatment Free Survival
Description	Kaplan-Meier methods and 95% confidence interval will be estimated using Greenwood's formula.
Time Frame	Up to 730 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Prostate-specific Antigen Progression Rate
Description	Prostate-specific antigen progression rate will be defined per Prostate Cancer Working Group 2 criteria (i.e. confirmed rising prostate-specific antigen >= 2 ng/mL at least one week apart) and will be computed along with 95% confidence interval.
Time Frame	At 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Prostate-specific Antigen Progression Free Survival as Defined by the Prostate Cancer Working Group 2 Criteria
Description	Prostate-specific antigen progression free survival will be estimated using Kaplan-Meier methods and 95% confidence interval will be estimated using Greenwood's formula.
Time Frame	At 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Change in Radiographic Disappearance of Magnetic Resonance Imaging Detectable Prostate Cancer
Description	This calculates the percentage of participants with radiographic disappearance of magnetic resonance imaging detectable prostate cancer. This is only in patients with a baseline nodule that is Prostate Imaging Reporting and Data System 3 or more and > 5 mm.
Time Frame	Baseline to up to 90 days

Outcome Measure Data

Analysis Population Description

Only 1 patient had paired MRI at baseline and again at post-treatment.

Arm/Group Title	Apalutamide
Arm/Group Description	Day 1 until Day 90. Patients receive apalutamide PO QD for 90 days in the absence of disease progression or unacceptable toxicity. Apalutamide: Given PO Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies
Measure Participants	1
Number [percentage of participants]	0 0%

9. Secondary Outcome

Title	Incidence of Adverse Events
Description	As assessed by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03.
Time Frame	Up to 730 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Secondary Outcome

Title	Severity of Adverse Events
Description	As assessed by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03.
Time Frame	Up to 730 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Secondary Outcome

Title	Change in Quality of Life: FACT-P Assessment
Description	As assessed using the Functional Assessment of Cancer Therapy-Prostate surveys. Functional Assessment of Cancer Therapy-Prostate is a validated quality of life survey specific for patients with prostate cancer.
Time Frame	Baseline to up to 730 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Secondary Outcome

Title	Change in Quality of Life: SF-36 Assessment
Description	As assessed using the Short Form-36 survey. Short Form-36 is a validated quality of life survey. This is a generic survey to assess an individual's overall well-being, and is not specific to one disease.
Time Frame	Baseline to up to 730 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	From Day 1 until Day 90.
Arm/Group Title	Apalutamide
Arm/Group Description	Day 1 until Day 90. Patients receive apalutamide PO QD for 90 days in the absence of disease progression or unacceptable toxicity. Apalutamide: Given PO Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies
All Cause Mortality
	Apalutamide
	Affected / at Risk (%)	# Events
Total	0/23 (0%)
Serious Adverse Events
	Apalutamide
	Affected / at Risk (%)	# Events
Total	0/23 (0%)
Other (Not Including Serious) Adverse Events
	Apalutamide
	Affected / at Risk (%)	# Events
Total	23/23 (100%)
Blood and lymphatic system disorders
Anemia	1/23 (4.3%)	1
Hypocalcemia	1/23 (4.3%)	1
Hypertension	1/23 (4.3%)	1
Cardiac disorders
Tachycardia	1/23 (4.3%)	1
Atrial Flutter	1/23 (4.3%)	1
Endocrine disorders
Hypothyroidism	1/23 (4.3%)	1
Eye disorders
Impaired Vision	1/23 (4.3%)	1
Gastrointestinal disorders
Nausea	2/23 (8.7%)	2
Rectal Hemorrhage	1/23 (4.3%)	1
Constipation	1/23 (4.3%)	1
Increased Bowel Movement Frequency	1/23 (4.3%)	1
Muscositis Oral	1/23 (4.3%)	1
Stomach Pain	1/23 (4.3%)	1
Dyspepsia	1/23 (4.3%)	1
Clostridium Difficile Enteritis	1/23 (4.3%)	1
General disorders
Fatigue/Decreased Energy	18/23 (78.3%)	18
Flu Like Symptoms	1/23 (4.3%)	1
Immune system disorders
Sinusitis	1/23 (4.3%)	1
Sore Throat	1/23 (4.3%)	1
Infections and infestations
Rhinorrhea	1/23 (4.3%)	1
Shingles	1/23 (4.3%)	1
Injury, poisoning and procedural complications
Fall	1/23 (4.3%)	1
Investigations
Increased/Elevated TSH	4/23 (17.4%)	4
Alanine Aminotransferase Increased	1/23 (4.3%)	1
Aspartate Aminotransferase Increased	2/23 (8.7%)	2
Metabolism and nutrition disorders
Weight Loss/Anorexia	5/23 (21.7%)	7
Musculoskeletal and connective tissue disorders
Arthralgia	6/23 (26.1%)	6
Edema	1/23 (4.3%)	1
Myalgia	2/23 (8.7%)	2
Cramp	1/23 (4.3%)	1
Akathisia	1/23 (4.3%)	1
Nervous system disorders
Dysgeusia	7/23 (30.4%)	7
Tingling	1/23 (4.3%)	1
Postural Dizziness/Balance Changes	4/23 (17.4%)	4
Lightheadedness	2/23 (8.7%)	2
Headache	1/23 (4.3%)	1
Psychiatric disorders
Insomnia	2/23 (8.7%)	2
Libido Decreased	5/23 (21.7%)	5
Labile Mood	1/23 (4.3%)	1
Cognitive Disturbance	1/23 (4.3%)	1
Memory Impairment/Forgetfulness/Amnesia	3/23 (13%)	3
Brain Fog	1/23 (4.3%)	1
Concentration Impairment	1/23 (4.3%)	1
Anxiety	1/23 (4.3%)	1
Decreased Mental Acuity	1/23 (4.3%)	1
Renal and urinary disorders
Lower Urinary Tract Symptoms	2/23 (8.7%)	2
Dribbling	1/23 (4.3%)	1
Hematuria	1/23 (4.3%)	1
Reproductive system and breast disorders
Gynecomastia	6/23 (26.1%)	6
Nipple Sensitivity/Tenderness	11/23 (47.8%)	11
Mastodynia	2/23 (8.7%)	2
Erectile Dysfunction	1/23 (4.3%)	1
Breast Tenderness	1/23 (4.3%)	1
Ejaculation Disorder	1/23 (4.3%)	1
Nipple Itchiness	1/23 (4.3%)	1
Perceived Shrinking of Genitals	1/23 (4.3%)	1
Testicle Pain	1/23 (4.3%)	1
Bronchitis	1/23 (4.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/23 (4.3%)	1
Upper Respiratory Infection Symptoms	2/23 (8.7%)	2
Chest Tightness	1/23 (4.3%)	1
Skin and subcutaneous tissue disorders
Erythema	1/23 (4.3%)	1
Pruritis	3/23 (13%)	3
Rash	7/23 (30.4%)	7
Dry Skin	3/23 (13%)	3
Cellulitis	1/23 (4.3%)	1
Lack of Body Odor	1/23 (4.3%)	1
Burning Sensation	1/23 (4.3%)	1
Painful Callus Bumps	1/23 (4.3%)	1
Vascular disorders
Hot Flashes	5/23 (21.7%)	5
Warmer Body	2/23 (8.7%)	2

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.