Clinical Trial of Oral Ciprofloxacin and Etoposide in Subjects With Resistant Acute Myeloid Leukemia (AML)(UF-AML-CE-101)

• Sponsor: University of Florida (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02773732
• Collaborator: (none)
• Enrollment: 11
• Location: 1
• Arms: 3
• Actual Duration (Months): 59
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of the first part of this study is to establish the maximum tolerated dose (MTD) of oral ciprofloxacin when given in combination with a fixed dose of oral etoposide in patients with resistant acute myeloid leukemia (AML). The purpose of the second part of this study is to determine if the established dose of oral ciprofloxacin in combination with oral etoposide is effective in the treatment of patients with resistant AML.

Condition or Disease	Intervention/Treatment	Phase
Leukemia; Acute Myelogenous Leukemia; Acute Myeloid Leukemia	Drug: Ciprofloxacin 750 MG; Drug: Etoposide; Drug: Ciprofloxacin 1000 MG; Drug: Ciprofloxacin 500 mg	Phase 1/Phase 2

Detailed Description

This study will look at: any side effects that occur, the effectiveness of the study drug, and how your disease reacts to ciprofloxacin in combination with etoposide. This study will try to find the highest tolerated dose of ciprofloxacin without causing serious side effects.

Ciprofloxacin is a commonly used antibiotic drug that is approved for use by the United States Food and Drug Administration (FDA). The FDA has not approved ciprofloxacin to treat AML. Etoposide is an anticancer chemotherapy drug that is approved for use by the FDA for the treatment of small cell lung cancer and testicular cancer. Etoposide is also used for treatment of various blood cancers.

There is laboratory research that has shown that ciprofloxacin can make leukemia cells more sensitive to etoposide chemotherapy. This observation indicates that ciprofloxacin may help improve the effectiveness of etoposide in the treatment of resistant AML.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase Ib/II Clinical Trial of Oral Ciprofloxacin and Etoposide in Subjects With Resistant Acute Myeloid Leukemia (AML)
• Actual Study Start Date: Dec 16, 2016
• Actual Primary Completion Date: Sep 7, 2021
• Actual Study Completion Date: Nov 15, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ciprofloxacin Dose Level 0	Drug: Ciprofloxacin 750 MG; 750 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle.; Other Names: Cipro ; Drug: Etoposide; Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle.; Other Names: VP-16 Vepesid
Experimental: Ciprofloxacin Dose Level +1	Drug: Etoposide; Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle.; Other Names: VP-16 Vepesid ; Drug: Ciprofloxacin 1000 MG; 1000 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle.; Other Names: Cipro
Experimental: Ciprofloxacin Dose Level -1	Drug: Etoposide; Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle.; Other Names: VP-16 Vepesid ; Drug: Ciprofloxacin 500 mg; 500 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle.; Other Names: Cipro

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose [1 month]

   Establish the maximum tolerated dose (MTD) of oral ciprofloxacin when given in combination with a fixed dose of oral Etoposide for the treatment of resistant AML.

2. Rate of Complete Remission [0 months]

   Determine the rate of complete remission (CR) following treatment with the MTD of oral ciprofloxacin in combination with oral Etoposide for the treatment of resistant AML.

Secondary Outcome Measures

1. Response Duration [111 days]

   Measure the response duration following treatment with oral ciprofloxacin in combination with oral etoposide for the treatment of resistant AML.

2. Progression-free Survival [317 days]

   Measure progression-free survival following treatment with oral ciprofloxacin in combination with oral Etoposide for the treatment of resistant AML.

3. Overall Survival [317 days]

   Measure overall survival following treatment with oral ciprofloxacin in combination with oral Etoposide for the treatment of resistant AML.

4. Percentage of Grade ≥ 3 Adverse Events [93 days]

   Estimate the rate of Grade ≥ 3 adverse events following treatment with oral ciprofloxacin and oral etoposide at the MTD.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Diagnosis of AML confirmed by review of bone marrow pathology at the University of Florida.

• Patients with relapsed and /or refractory AML who: failed to achieve complete remission (CR) or complete remission with incomplete blood count recovery (CRi) after at least one cycle of induction chemotherapy and not suitable for a second cycle of standard intensive chemotherapy; or who have progressed after 1 cycle of hypomethylating agent or intolerant to hypomethylating agent therapy and not suitable for standard induction chemotherapy regimens; or have relapsed after any duration of response.

• Per the treating physician, the subject must have a life expectancy of >= 4 weeks.

• Subject performance status must be Eastern Cooperative Oncology Group (ECOG) 0, 1, or

• Subject must have a total bilirubin <= 2 mg/dL and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5 times the upper limit of normal.

• Subject must have serum creatinine < 2 mg/dL.

• Females of child-bearing potential may participate, provided they meet the following conditions: Must agree to use physician-approved contraceptive methods throughout the study and for 6 months following the last dose of ciprofloxacin and/or etoposide; Must have a negative serum pregnancy test within 7 days prior to beginning treatment on this study.

• Males with female partners of child-bearing potential must agree to use physician-approved contraceptive methods throughout the study and should avoid conceiving children for 6 months following the last dose of ciprofloxacin and/or etoposide.

• Must provide written informed consent and be willing to comply with all study-related procedures.

Exclusion Criteria:

• History of allergic or significant adverse reaction [e.g., anaphylaxis, prolonged QTc, or severe tendonitis] to ciprofloxacin or etoposide.

• Acute promyelocytic leukemia (APL) with t(15;17).

• Prolonged baseline QTc, defined as QTc interval > 470 msec in women and > 450 msec in men, or > 480 msec in subjects with a bundle branch block.

• Uncontrolled, clinically significant infection. Subjects with a fever (temperature >= 38.3) thought to be related to leukemia are eligible assuming that blood cultures are negative during the 7 days prior to Cycle 1 Day 1 and there is no clinical evidence of active infection (e.g., negative or stable radiographs and negative physical examination).

• Ongoing, symptomatic Clostridium difficile infection. Subjects who are asymptomatic with negative stool for C. difficile may participate.

• Pregnant and or nursing.

• History of Myasthenia Gravis.

• Treatment with any anticancer therapy (standard or investigational) within 14 days prior to the first dose of ciprofloxacin or less than full recovery from the clinically significant toxic effects of that treatment. The use of hydroxyurea is allowed only during the first 14 days of Cycle 1.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UF Health Shands Cancer Hospital	Gainesville	Florida	United States	32608

Sponsors and Collaborators

• University of Florida

Investigators

• Principal Investigator: Randall Brown, MD, University of Florida

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 30, 2020

More Information

Publications

None provided.

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT02773732
• Other Study ID Numbers: IRB201600693; UF-AML-CE-101; OCR14651
• First Posted: May 16, 2016
• Last Update Posted: Aug 5, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Ciprofloxacin; Etoposide

Study Results

Participant Flow

Arm/Group Title	Ciprofloxacin Dose Level 0	Ciprofloxacin Dose Level +1
Arm/Group Description	750 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle. Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle.	1000 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle. Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle.
Period Title: Ciprofloxacin Dose Level 0
STARTED	3	0
COMPLETED	3	0
NOT COMPLETED	0	0
Period Title: Ciprofloxacin Dose Level 0
STARTED	0	8
COMPLETED	0	8
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Ciprofloxacin Dose Level 0	Ciprofloxacin Dose Level +1	Total
Arm/Group Description	750 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle. Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle.	1000 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle. Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle.	Total of all reporting groups
Overall Participants	3	8	11
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	1 33.3%	4 50%	5 45.5%
>=65 years	2 66.7%	4 50%	6 54.5%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	68.67	61.75	63.64
Sex: Female, Male (Count of Participants)
Female	1 33.3%	3 37.5%	4 36.4%
Male	2 66.7%	5 62.5%	7 63.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	3 100%	8 100%	11 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 33.3%	2 25%	3 27.3%
White	2 66.7%	5 62.5%	7 63.6%
More than one race	0 0%	1 12.5%	1 9.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	3 100%	8 100%	11 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose
Description	Establish the maximum tolerated dose (MTD) of oral ciprofloxacin when given in combination with a fixed dose of oral Etoposide for the treatment of resistant AML.
Time Frame	1 month

Outcome Measure Data

Analysis Population Description

2 subjects were not evaluable for this outcome measure.

Arm/Group Title	Ciprofloxacin and Etoposide
Arm/Group Description	Ciprofloxacin: Ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle. Dose Level 0 Ciprofloxacin 750 mg Dose Level +1 Ciprofloxacin 1000 mg Dose Level -1 Ciprofloxacin 500 mg Etoposide: Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle.
Measure Participants	9
Number [milligrams]	1000

2. Primary Outcome

Title	Rate of Complete Remission
Description	Determine the rate of complete remission (CR) following treatment with the MTD of oral ciprofloxacin in combination with oral Etoposide for the treatment of resistant AML.
Time Frame	0 months

Outcome Measure Data

Analysis Population Description

No participants were analyzed for this outcome measure because the study did not proceed to phase II.

Arm/Group Title	Ciprofloxacin and Etoposide
Arm/Group Description	Ciprofloxacin: Ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle. Dose Level 0 Ciprofloxacin 750 mg Dose Level +1 Ciprofloxacin 1000 mg Dose Level -1 Ciprofloxacin 500 mg Etoposide: Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle.
Measure Participants	0

3. Secondary Outcome

Title	Response Duration
Description	Measure the response duration following treatment with oral ciprofloxacin in combination with oral etoposide for the treatment of resistant AML.
Time Frame	111 days

Outcome Measure Data

Analysis Population Description

Only 1 participant in the ciprofloxacin Dose Level +1 cohort had a response to measure response duration.

Arm/Group Title	Ciprofloxacin Dose Level +1
Arm/Group Description	1000 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle. Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle.
Measure Participants	1
Number [days]	111

4. Secondary Outcome

Title	Progression-free Survival
Description	Measure progression-free survival following treatment with oral ciprofloxacin in combination with oral Etoposide for the treatment of resistant AML.
Time Frame	317 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ciprofloxacin Dose Level 0	Ciprofloxacin Dose Level +1
Arm/Group Description	750 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle. Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle.	1000 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle. Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle
Measure Participants	3	8
Mean (Full Range) [days]	56	92.25

5. Secondary Outcome

Title	Overall Survival
Description	Measure overall survival following treatment with oral ciprofloxacin in combination with oral Etoposide for the treatment of resistant AML.
Time Frame	317 days

Outcome Measure Data

Analysis Population Description

1 subject was still alive at the time protocol follow-up was discontinued, so they are not included in the analysis for this outcome measure.

Arm/Group Title	Ciprofloxacin Dose Level 0	Ciprofloxacin Dose Level +1
Arm/Group Description	750 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle. Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle.	1000 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle. Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle.
Measure Participants	3	7
Mean (Full Range) [days]	140.67	109.29

6. Secondary Outcome

Title	Percentage of Grade ≥ 3 Adverse Events
Description	Estimate the rate of Grade ≥ 3 adverse events following treatment with oral ciprofloxacin and oral etoposide at the MTD.
Time Frame	93 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ciprofloxacin Dose Level 0	Ciprofloxacin Dose Level +1
Arm/Group Description	750 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle. Etoposide: Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle.	1000 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle. Etoposide: Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle.
Measure Participants	3	8
Number [percentage of reported adverse events]	20	28.45

Adverse Events

Time Frame	At minimum, adverse event data were collected at screening, every 7 days during study treatment and at 28 days after the last dose of study treatment. Adverse event data were collected for a maximum of 93 days for all participants. All-cause mortality data was collected over a maximum of 317 days for all participants.
Adverse Event Reporting Description	Adverse events were assessed by the principal investigator, the treating sub-investigator, and/or the study coordinator at screening, every 7 days during study treatment, and at 28 days after the last dose of study treatment at a minimum. Adverse events were assessed by physical examination, labs, and subject self-reports.
Arm/Group Title	Ciprofloxacin Dose Level 0		Ciprofloxacin Dose Level +1
Arm/Group Description	750 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle. Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle.		1000 mg ciprofloxacin will be taken orally twice daily on Days 1 to 10 of each 28-day cycle. Etoposide 200 mg will be taken orally once daily on Days 2 to 8 of each 28-day cycle.
All Cause Mortality
	Ciprofloxacin Dose Level 0		Ciprofloxacin Dose Level +1
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		7/8 (87.5%)
Serious Adverse Events
	Ciprofloxacin Dose Level 0		Ciprofloxacin Dose Level +1
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		4/8 (50%)
Blood and lymphatic system disorders
Febrile neutropenia	1/3 (33.3%)		3/8 (37.5%)
Cardiac disorders
Cardiac disorders - other, specify	1/3 (33.3%)		0/8 (0%)
Gastrointestinal disorders
Abdominal pain	1/3 (33.3%)		0/8 (0%)
Diarrhea	0/3 (0%)		1/8 (12.5%)
General disorders
Fever	1/3 (33.3%)		0/8 (0%)
Metabolism and nutrition disorders
Metabolism and nutrition disorders - other, specify	0/3 (0%)		1/8 (12.5%)
Dehydration	0/3 (0%)		1/8 (12.5%)
Nervous system disorders
Encephalopathy	0/3 (0%)		1/8 (12.5%)
Other (Not Including Serious) Adverse Events
	Ciprofloxacin Dose Level 0		Ciprofloxacin Dose Level +1
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		7/8 (87.5%)
Blood and lymphatic system disorders
Anemia	2/3 (66.7%)		5/8 (62.5%)
Leukocytosis	1/3 (33.3%)		1/8 (12.5%)
Lymph node pain	1/3 (33.3%)		0/8 (0%)
Cardiac disorders
Cardiac disorders - other, specify	0/3 (0%)		1/8 (12.5%)
Palpitations	1/3 (33.3%)		0/8 (0%)
Sinus tachycardia	1/3 (33.3%)		1/8 (12.5%)
Ear and labyrinth disorders
Ear pain	0/3 (0%)		1/8 (12.5%)
Eye disorders
Eye pain	1/3 (33.3%)		0/8 (0%)
Photophobia	1/3 (33.3%)		0/8 (0%)
Gastrointestinal disorders
Abdominal pain	1/3 (33.3%)		2/8 (25%)
Diarrhea	1/3 (33.3%)		3/8 (37.5%)
Dyspepsia	0/3 (0%)		1/8 (12.5%)
Gastrointestinal disorders - other, specify	0/3 (0%)		1/8 (12.5%)
Gastrointestinal disorders - other, specify	0/3 (0%)		1/8 (12.5%)
Gastrointestinal disorders - other, specify	0/3 (0%)		1/8 (12.5%)
Gastrointestinal pain	0/3 (0%)		1/8 (12.5%)
Hemorrhoids	0/3 (0%)		1/8 (12.5%)
Mucositis oral	0/3 (0%)		1/8 (12.5%)
Nausea	1/3 (33.3%)		4/8 (50%)
Oral pain	0/3 (0%)		1/8 (12.5%)
Vomiting	1/3 (33.3%)		3/8 (37.5%)
General disorders
Chills	0/3 (0%)		1/8 (12.5%)
Edema face	0/3 (0%)		1/8 (12.5%)
Edema limbs	1/3 (33.3%)		1/8 (12.5%)
Fatigue	2/3 (66.7%)		4/8 (50%)
Non-cardiac chest pain	0/3 (0%)		1/8 (12.5%)
Pain	1/3 (33.3%)		0/8 (0%)
Infections and infestations
Lung infection	1/3 (33.3%)		2/8 (25%)
Mucosal infection	0/3 (0%)		1/8 (12.5%)
Sinusitis	1/3 (33.3%)		0/8 (0%)
Skin infection	0/3 (0%)		1/8 (12.5%)
Upper respiratory infection	1/3 (33.3%)		0/8 (0%)
Urinary tract infection	0/3 (0%)		2/8 (25%)
Injury, poisoning and procedural complications
Fall	0/3 (0%)		1/8 (12.5%)
Investigations
Alanine aminotransferase increased	0/3 (0%)		1/8 (12.5%)
Alkaline phosphatase increased	0/3 (0%)		1/8 (12.5%)
Aspartate aminotransferase increased	0/3 (0%)		2/8 (25%)
Blood bilirubin increased	0/3 (0%)		2/8 (25%)
Creatinine increased	1/3 (33.3%)		4/8 (50%)
Electrocardiogram QT corrected interval prolonged	0/3 (0%)		1/8 (12.5%)
Investigations - Other, specify	0/3 (0%)		1/8 (12.5%)
Investigations - Other, specify	0/3 (0%)		1/8 (12.5%)
Lymphocyte count decreased	0/3 (0%)		3/8 (37.5%)
Neutrophil count decreased	1/3 (33.3%)		3/8 (37.5%)
Platelet count decreased	1/3 (33.3%)		5/8 (62.5%)
White blood cell decreased	1/3 (33.3%)		5/8 (62.5%)
Metabolism and nutrition disorders
Anorexia	1/3 (33.3%)		2/8 (25%)
Dehydration	2/3 (66.7%)		0/8 (0%)
Hypercalcemia	0/3 (0%)		1/8 (12.5%)
Hyperglycemia	0/3 (0%)		1/8 (12.5%)
Hyperkalemia	1/3 (33.3%)		0/8 (0%)
Hyperuricemia	1/3 (33.3%)		4/8 (50%)
Hypoalbuminemia	0/3 (0%)		3/8 (37.5%)
Hypocalcemia	1/3 (33.3%)		2/8 (25%)
Hypokalemia	1/3 (33.3%)		3/8 (37.5%)
Hypomagnesemia	0/3 (0%)		4/8 (50%)
Hyponatremia	0/3 (0%)		3/8 (37.5%)
Hypophosphatemia	1/3 (33.3%)		5/8 (62.5%)
Musculoskeletal and connective tissue disorders
Generalized muscle weakness	2/3 (66.7%)		0/8 (0%)
Musculoskeletal and connective tissue disorder - Other, specify	0/3 (0%)		1/8 (12.5%)
Neck pain	1/3 (33.3%)		1/8 (12.5%)
Pain in extremity	0/3 (0%)		2/8 (25%)
Nervous system disorders
Dizziness	3/3 (100%)		1/8 (12.5%)
Dysgeusia	0/3 (0%)		1/8 (12.5%)
Headache	1/3 (33.3%)		0/8 (0%)
Tremor	1/3 (33.3%)		0/8 (0%)
Psychiatric disorders
Confusion	1/3 (33.3%)		0/8 (0%)
Insomnia	1/3 (33.3%)		0/8 (0%)
Renal and urinary disorders
Hematuria	0/3 (0%)		1/8 (12.5%)
Renal and urinary disorders - Other, specify	0/3 (0%)		1/8 (12.5%)
Urinary frequency	2/3 (66.7%)		0/8 (0%)
Urinary tract pain	0/3 (0%)		1/8 (12.5%)
Respiratory, thoracic and mediastinal disorders
Cough	1/3 (33.3%)		1/8 (12.5%)
Dyspnea	1/3 (33.3%)		1/8 (12.5%)
Epistaxis	0/3 (0%)		3/8 (37.5%)
Nasal congestion	0/3 (0%)		1/8 (12.5%)
Sore throat	0/3 (0%)		1/8 (12.5%)
Skin and subcutaneous tissue disorders
Alopecia	0/3 (0%)		2/8 (25%)
Hyperhidrosis	0/3 (0%)		1/8 (12.5%)
Skin and subcutaneous tissue disorders - Other, specify	0/3 (0%)		1/8 (12.5%)
Skin hypopigmentation	0/3 (0%)		1/8 (12.5%)
Skin ulceration	0/3 (0%)		2/8 (25%)
Vascular disorders
Hematoma	0/3 (0%)		1/8 (12.5%)
Hypotension	2/3 (66.7%)		1/8 (12.5%)

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.