Armodafinil in Treating Fatigue Caused By Radiation Therapy in Patients With Primary Brain Tumors

• Sponsor: Wake Forest University Health Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT01032200
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 54
• Location: 1
• Arms: 2
• Actual Duration (Months): 29.3
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

RATIONALE: Armodafinil may help relieve fatigue and improve quality of life in patients with cancer receiving radiation therapy to the brain.

PURPOSE: This clinical trial is studying how well armodafinil works in treating fatigue caused by radiation therapy in patients with primary brain tumors.

Condition or Disease	Intervention/Treatment	Phase
Brain Tumors; Nervous System Tumors; Cognition Disorders; Fatigue	Drug: Armodafinil; Other: placebo	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To estimate study accrual, adherence, retention, and participation of patients with primary brain tumors undergoing partial- or whole-brain radiotherapy who are randomized to receive armodafinil or placebo.

• To estimate the variability of fatigue, quality of life, and neurocognitive function in these patients.

Secondary

• To obtain a preliminary estimate of the effect of armodafinil on fatigue as measured by the fatigue subscale of the FACIT-F and the Brief Fatigue Inventory.

• To estimate the rates of toxicity and adverse events associated with armodafinil.

• To obtain preliminary estimates of the effect of armodafinil on sleepiness as measured by the Epworth Sleep Scale; overall quality of life and brain-specific quality of life as measured by the FACT-G with the brain subscale; and cognitive function as measured by a comprehensive Wake Forest Cognitive Function Battery.

OUTLINE: This is a multicenter study. Patients are stratified according to therapy (radiotherapy alone vs radiotherapy and chemotherapy) and Karnofsky performance status (60-80% vs 90-100%). Patients are randomized to 1 of 2 arms.

• Arm I: Patients receive oral armodafinil once daily beginning no later than the fifth fraction of brain radiotherapy and continuing for 9-11 weeks in the absence of unacceptable toxicity.

• Arm II: Patients receive oral placebo once daily beginning no later than the fifth fraction of brain radiotherapy and continuing for 9-11 weeks in the absence of unacceptable toxicity.

Patients complete questionnaires assessing fatigue, quality of life, and neurocognitive function at baseline and periodically during study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: A Feasibility Study of Armodafinil for Brain Radiation-Induced Fatigue
• Actual Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Jan 8, 2013
• Actual Study Completion Date: Jan 8, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I - Armodafinil Patients receive oral armodafinil once daily beginning no later than the fifth fraction of brain radiotherapy and continuing for 9-11 weeks in the absence of unacceptable toxicity.	Drug: Armodafinil; Given orally
Placebo Comparator: Arm II - Placebo Patients receive oral placebo once daily beginning no later than the fifth fraction of brain radiotherapy and continuing for 9-11 weeks in the absence of unacceptable toxicity.	Other: placebo; Given orally

Outcome Measures

Primary Outcome Measures

1. Retention [4 weeks post-RT (approximately 3 months post randomization)]

   Retention is defined as the percentage of participants who complete the 4 week post-RT questionnaires.

2. Adherence [4 weeks post-RT (approximately 3 months post randomization)]

   Adherence is the percentage of ideal number of pills taken while on study (based on returned diaries)

Secondary Outcome Measures

1. Fatigue [4 weeks post-RT]

   Fatigue is measured by the fatigue subscale of the Functional Assessment of Chronic Illness Therapy Questionnaire. It consists of 13 questions each answered on a 0 to 4 scale. The fatigue score is the sum of the responses with some questions reverse scored. The total Score ranges from 0 to 52, with higher scores indicating less fatigue.

2. Sleepiness [4 weeks post-RT]

   Sleepiness as measured by the Epworth Sleep Scale. It consists of 8 questions that measure daytime sleepiness in which the patient records their likelihood of dozing or sleeping during a number of routine daily activities. ESS scores range from 0 to 24. Higher scores denote greater sleepiness.

3. HVLT-IR [4 weeks post-RT]

   HVLT-IR is the Hopkins Verbal learning test - immediate recall. Participants are given 12 words to remember. They are then asked to recall those words. This is repeated 3 times. Minimum recalled words 0 maximum 36. The HVLT-IR score is the sum of correctly recalled words across the three trials. Higher scores indicate better recall.

Eligibility Criteria

Criteria

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

Inclusion Criteria

• Histologically confirmed primary brain tumor, including any of the following:

• Glioblastoma multiforme

• Anaplastic astrocytoma

• Anaplastic oligodendroglioma

• Anaplastic mixed oligoastrocytoma

• Low-grade glioma

• Meningioma

• Ependymoma

• Other primary brain tumor histologies

• Planning to undergo external-beam cranial radiotherapy (partial- or whole-brain radiotherapy) meeting all of the following criteria:

• Total dose ≥ 4,500 cGy

• Total number of fractions ≥ 25 fractions

• Dose per fraction ≥ 150 cGy

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%

• Hemoglobin ≥ 10.0 g/dL (erythropoietin or transfusion allowed for symptomatically anemic patients with a hemoglobin < 10 g/dL)

• Creatinine ≤ 2 mg/dL

• Total bilirubin ≤ 2 times upper limit of normal (ULN)

• SGOT and SGPT ≤ 3 times ULN

• Not pregnant or nursing

• Negative pregnancy test

• Sexually active women of childbearing potential must use a reliable method of birth control

• It is recommended that patients use non-hormonal contraceptives, in addition to or in place of hormonal contraceptives, during and for one month following treatment with armodafinil

• Prior malignancies allowed

Exclusion Criteria:

• No baseline headaches (i.e., headaches occurring in the week before baseline assessment) of grade 4 severity (defined as severe and disabling headaches, requiring analgesics, and interfering with and preventing function or activities of daily living)

• No concurrent uncontrolled illness that may cause fatigue; interfere with drug absorption, distribution, metabolism, or excretion; or limit compliance with study requirements including, but not limited to, any of the following:

• Ongoing or active infection

• Chronic renal insufficiency

• Psychiatric illness (psychosis, psychotic disorder, history of suicide attempt, or actively suicidal)

• Extreme social situations (e.g., transportation issues that would preclude study compliance)

• Patients with a history of cardiac issues (symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia) should not use armodafinil as it may cause chest pain, palpitations, dyspnea, and transient ischemic T-wave changes on ECG

• No history of allergic reaction attributed to modafinil or armodafinil

• No anticipated or planned excessive consumption of coffee, tea, and/or caffeine-containing beverages averaging > 600 mg of caffeine/day (i.e., approximately 6 cups of coffee/day, 12 cups of hot tea/day, or 12 cans of cola/day)

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior fractionated external-beam cranial radiotherapy

• More than 30 days since prior monoamine oxidate inhibitors or investigational drugs

• More than 2 weeks since prior and no concurrent modafinil (Provigil), donepezil (Aricept), memantine hydrochloride (Namenda), methylphenidate (Ritalin), dextroamphetamine-amphetamine (Adderall), ginkgo biloba, or any other cognitive function-enhancing drugs

• At least 4 weeks since prior and no concurrent interstitial or intracavitary chemotherapy and/or radiotherapy or stereotactic radiosurgery (i.e., Gamma Knife, Linac, or Cyberknife)

• No concurrent erythropoietin, transfusion, or iron therapy (unless patient is symptomatically anemic with hemoglobin < 10 g/dL)

• Concurrent chemotherapy allowed

• Concurrent hormonal therapy for other malignancies allowed

• No concurrent non-hormonal therapy (e.g., Herceptin and other targeted agents), or cytotoxic chemotherapy

• No concurrent clopidogrel bisulfate (Plavix)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157-1096

Sponsors and Collaborators

• Wake Forest University Health Sciences
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Edward G. Shaw, MD, Wake Forest University Health Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT01032200
• Other Study ID Numbers: IRB00012856; U10CA081851; REBACCCWFU97509
• First Posted: Dec 15, 2009
• Last Update Posted: Sep 28, 2021
• Last Verified: Sep 1, 2021

• 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
• Keywords provided by Wake Forest University Health Sciences: fatigue; cognitive/functional effects; adult giant cell glioblastoma; adult glioblastoma; adult gliosarcoma; adult anaplastic astrocytoma; adult anaplastic oligodendroglioma; adult mixed glioma; adult diffuse astrocytoma; adult pilocytic astrocytoma; adult pineal gland astrocytoma; adult subependymal giant cell astrocytoma; adult oligodendroglioma; adult anaplastic ependymoma; adult ependymoma; adult myxopapillary ependymoma; adult subependymoma; adult anaplastic meningioma; adult grade I meningioma; adult grade II meningioma; adult grade III meningioma; adult papillary meningioma; adult brain stem glioma
• Additional relevant MeSH terms: Neoplasms; Brain Neoplasms; Nervous System Neoplasms; Fatigue; Cognition Disorders; Modafinil

Study Results

Participant Flow

Arm/Group Title	Arm I - Armodafinil	Arm II - Placebo
Arm/Group Description	Patients receive oral armodafinil once daily beginning no later than the fifth fraction of brain radiotherapy and continuing for 9-11 weeks in the absence of unacceptable toxicity. Armodafinil: Given orally	Patients receive oral placebo once daily beginning no later than the fifth fraction of brain radiotherapy and continuing for 9-11 weeks in the absence of unacceptable toxicity. placebo: Given orally
Period Title: Overall Study
STARTED	26	28
COMPLETED	22	21
NOT COMPLETED	4	7

Baseline Characteristics

Arm/Group Title	Arm I - Armodafinil	Arm II - Placebo	Total
Arm/Group Description	Patients receive oral armodafinil once daily beginning no later than the fifth fraction of brain radiotherapy and continuing for 9-11 weeks in the absence of unacceptable toxicity. Armodafinil: Given orally	Patients receive oral placebo once daily beginning no later than the fifth fraction of brain radiotherapy and continuing for 9-11 weeks in the absence of unacceptable toxicity. placebo: Given orally	Total of all reporting groups
Overall Participants	26	28	54
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	19 73.1%	18 64.3%	37 68.5%
>=65 years	7 26.9%	10 35.7%	17 31.5%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	59	58	59
Sex: Female, Male (Count of Participants)
Female	14 53.8%	15 53.6%	29 53.7%
Male	12 46.2%	13 46.4%	25 46.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 3.8%	0 0%	1 1.9%
Not Hispanic or Latino	25 96.2%	28 100%	53 98.1%
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%	1 3.6%	1 1.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	2 7.1%	2 3.7%
White	26 100%	25 89.3%	51 94.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	26 100%	28 100%	54 100%

Outcome Measures

1. Primary Outcome

Title	Retention
Description	Retention is defined as the percentage of participants who complete the 4 week post-RT questionnaires.
Time Frame	4 weeks post-RT (approximately 3 months post randomization)

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Arm I - Armodafinil	Arm II - Placebo
Arm/Group Description	Patients receive oral armodafinil once daily beginning no later than the fifth fraction of brain radiotherapy and continuing for 9-11 weeks in the absence of unacceptable toxicity. Armodafinil: Given orally	Patients receive oral placebo once daily beginning no later than the fifth fraction of brain radiotherapy and continuing for 9-11 weeks in the absence of unacceptable toxicity. placebo: Given orally
Measure Participants	26	28
Number [percentage of participants]	85 326.9%	75 267.9%

2. Primary Outcome

Title	Adherence
Description	Adherence is the percentage of ideal number of pills taken while on study (based on returned diaries)
Time Frame	4 weeks post-RT (approximately 3 months post randomization)

Outcome Measure Data

Analysis Population Description

Participants who returned pill diaries

Arm/Group Title	Arm I - Armodafinil	Arm II - Placebo
Arm/Group Description	Patients receive oral armodafinil once daily beginning no later than the fifth fraction of brain radiotherapy and continuing for 9-11 weeks in the absence of unacceptable toxicity. Armodafinil: Given orally	Patients receive oral placebo once daily beginning no later than the fifth fraction of brain radiotherapy and continuing for 9-11 weeks in the absence of unacceptable toxicity. placebo: Given orally
Measure Participants	22	25
Mean (Full Range) [percentage of ideal number of pills]	92.6	95.7

3. Secondary Outcome

Title	Fatigue
Description	Fatigue is measured by the fatigue subscale of the Functional Assessment of Chronic Illness Therapy Questionnaire. It consists of 13 questions each answered on a 0 to 4 scale. The fatigue score is the sum of the responses with some questions reverse scored. The total Score ranges from 0 to 52, with higher scores indicating less fatigue.
Time Frame	4 weeks post-RT

Outcome Measure Data

Analysis Population Description

Participants with any data

Arm/Group Title	Arm I - Armodafinil	Arm II - Placebo
Arm/Group Description	Patients receive oral armodafinil once daily beginning no later than the fifth fraction of brain radiotherapy and continuing for 9-11 weeks in the absence of unacceptable toxicity. Armodafinil: Given orally	Patients receive oral placebo once daily beginning no later than the fifth fraction of brain radiotherapy and continuing for 9-11 weeks in the absence of unacceptable toxicity. placebo: Given orally
Measure Participants	26	27
Least Squares Mean (Standard Error) [units on a scale]	32.4 (2.6)	36.4 (2.5)

4. Secondary Outcome

Title	Sleepiness
Description	Sleepiness as measured by the Epworth Sleep Scale. It consists of 8 questions that measure daytime sleepiness in which the patient records their likelihood of dozing or sleeping during a number of routine daily activities. ESS scores range from 0 to 24. Higher scores denote greater sleepiness.
Time Frame	4 weeks post-RT

Outcome Measure Data

Analysis Population Description

Participants with any data

Arm/Group Title	Arm I - Armodafinil	Arm II - Placebo
Arm/Group Description	Patients receive oral armodafinil once daily beginning no later than the fifth fraction of brain radiotherapy and continuing for 9-11 weeks in the absence of unacceptable toxicity. Armodafinil: Given orally	Patients receive oral placebo once daily beginning no later than the fifth fraction of brain radiotherapy and continuing for 9-11 weeks in the absence of unacceptable toxicity. placebo: Given orally
Measure Participants	26	27
Least Squares Mean (Standard Error) [units on a scale]	7.2 (1.0)	8.3 (1.0)

5. Secondary Outcome

Title	HVLT-IR
Description	HVLT-IR is the Hopkins Verbal learning test - immediate recall. Participants are given 12 words to remember. They are then asked to recall those words. This is repeated 3 times. Minimum recalled words 0 maximum 36. The HVLT-IR score is the sum of correctly recalled words across the three trials. Higher scores indicate better recall.
Time Frame	4 weeks post-RT

Outcome Measure Data

Analysis Population Description

Participants with any data

Arm/Group Title	Arm I - Armodafinil	Arm II - Placebo
Arm/Group Description	Patients receive oral armodafinil once daily beginning no later than the fifth fraction of brain radiotherapy and continuing for 9-11 weeks in the absence of unacceptable toxicity. Armodafinil: Given orally	Patients receive oral placebo once daily beginning no later than the fifth fraction of brain radiotherapy and continuing for 9-11 weeks in the absence of unacceptable toxicity. placebo: Given orally
Measure Participants	26	27
Least Squares Mean (Standard Error) [number of correctly recalled words]	21.2 (1.5)	20.0 (1.4)

Adverse Events

Time Frame	3 months
Adverse Event Reporting Description	The denominator for adverse events in each arm is the number of participants who provided post-treatment data.
Arm/Group Title	Arm I - Armodafinil		Arm II - Placebo
Arm/Group Description	Patients receive oral armodafinil once daily beginning no later than the fifth fraction of brain radiotherapy and continuing for 9-11 weeks in the absence of unacceptable toxicity. Armodafinil: Given orally		Patients receive oral placebo once daily beginning no later than the fifth fraction of brain radiotherapy and continuing for 9-11 weeks in the absence of unacceptable toxicity. placebo: Given orally
All Cause Mortality
	Arm I - Armodafinil		Arm II - Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/26 (3.8%)		2/28 (7.1%)
Serious Adverse Events
	Arm I - Armodafinil		Arm II - Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/26 (38.5%)		8/27 (29.6%)
Blood and lymphatic system disorders
Anemia	1/26 (3.8%)	1	0/27 (0%)	0
Febrile Neutropenia	1/26 (3.8%)	1	0/27 (0%)	0
Cardiac disorders
Acute Coronary Syndrome	0/26 (0%)	0	1/27 (3.7%)	1
Chest Pain	1/26 (3.8%)	1	1/27 (3.7%)	1
Hypertension	1/26 (3.8%)	1	0/27 (0%)	0
Eye disorders
Optic Nerve Disorder	1/26 (3.8%)	3	0/27 (0%)	0
photophobia	1/26 (3.8%)	1	0/27 (0%)	0
Gastrointestinal disorders
Diarrhea	1/26 (3.8%)	1	0/27 (0%)	0
Nausea	1/26 (3.8%)	1	2/27 (7.4%)	2
Vomiting	1/26 (3.8%)	1	0/27 (0%)	0
General disorders
Agitation	0/26 (0%)	0	2/27 (7.4%)	2
Anxiety	1/26 (3.8%)	1	1/27 (3.7%)	2
Death NOS	0/26 (0%)	0	1/27 (3.7%)	1
Delirium	0/26 (0%)	0	1/27 (3.7%)	1
Dizziness	1/26 (3.8%)	1	0/27 (0%)	0
Fall	1/26 (3.8%)	1	0/27 (0%)	0
Fatigue	0/26 (0%)	0	1/27 (3.7%)	3
Pain	0/26 (0%)	0	1/27 (3.7%)	1
Hepatobiliary disorders
Alanine Aminotransferase Increased	0/26 (0%)	0	1/27 (3.7%)	1
Infections and infestations
Infections and Infestations - Other	0/26 (0%)	0	2/27 (7.4%)	2
Lung Infection	1/26 (3.8%)	1	1/27 (3.7%)	1
Urinary Tract Infection	0/26 (0%)	0	1/27 (3.7%)	1
Metabolism and nutrition disorders
Hypoglycemia	0/26 (0%)	0	1/27 (3.7%)	1
Musculoskeletal and connective tissue disorders
Muscle Weakness - left-sided	0/26 (0%)	0	1/27 (3.7%)	1
Muscle Weakness - lower limb	0/26 (0%)	0	1/27 (3.7%)	1
Nervous system disorders
Headache	2/26 (7.7%)	2	1/27 (3.7%)	2
Psychiatric disorders
Confusion	1/26 (3.8%)	1	0/27 (0%)	0
Depression	0/26 (0%)	0	1/27 (3.7%)	2
Personality Change	0/26 (0%)	0	1/27 (3.7%)	1
Renal and urinary disorders
Hematuria	1/26 (3.8%)	1	0/27 (0%)	0
Vascular disorders
Stroke	1/26 (3.8%)	1	0/27 (0%)	0
Thromboembolic Event	1/26 (3.8%)	1	0/27 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm I - Armodafinil		Arm II - Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/26 (100%)		27/27 (100%)
Cardiac disorders
Hypertension	3/26 (11.5%)	7	5/27 (18.5%)	21
Ear and labyrinth disorders
Dizziness	9/26 (34.6%)	24	8/27 (29.6%)	32
Ear and Labyrinth - Other	0/26 (0%)	0	2/27 (7.4%)	2
Eye disorders
Blurred Vision	4/26 (15.4%)	11	2/27 (7.4%)	3
Eye Disorders - Other	5/26 (19.2%)	15	0/27 (0%)	0
Gastrointestinal disorders
Constipation	4/26 (15.4%)	6	4/27 (14.8%)	7
Diarrhea	0/26 (0%)	0	3/27 (11.1%)	4
Dry Mouth	9/26 (34.6%)	32	9/27 (33.3%)	45
Dyspepsia	2/26 (7.7%)	2	0/27 (0%)	0
Nausea	12/26 (46.2%)	35	13/27 (48.1%)	23
General disorders
Back Pain	2/26 (7.7%)	3	3/27 (11.1%)	7
Edema Limbs	0/26 (0%)	0	2/27 (7.4%)	2
Fatigue	17/26 (65.4%)	95	17/27 (63%)	71
Gait Disturbance	0/26 (0%)	0	2/27 (7.4%)	2
Headache	19/26 (73.1%)	93	16/27 (59.3%)	53
Localized Edema	2/26 (7.7%)	12	3/27 (11.1%)	15
Pain	3/26 (11.5%)	10	2/27 (7.4%)	2
Infections and infestations
Mucosal Infection	4/26 (15.4%)	16	0/27 (0%)	0
Sinusitis	0/26 (0%)	0	3/27 (11.1%)	3
Investigations
Investigations - Other	0/26 (0%)	0	2/27 (7.4%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	3/26 (11.5%)	6	7/27 (25.9%)	18
Generalized Muscle Weakness	0/26 (0%)	0	3/27 (11.1%)	8
Nervous system disorders
Tremor	0/26 (0%)	0	2/27 (7.4%)	11
Psychiatric disorders
Anxiety	15/26 (57.7%)	55	10/27 (37%)	39
Cognitive Disturbance	0/26 (0%)	0	2/27 (7.4%)	10
Confusion	3/26 (11.5%)	21	0/27 (0%)	0
Insomnia	12/26 (46.2%)	46	14/27 (51.9%)	63
Memory Impairment	0/26 (0%)	0	5/27 (18.5%)	17
Renal and urinary disorders
Urinary Frequency	0/26 (0%)	0	2/27 (7.4%)	8
Respiratory, thoracic and mediastinal disorders
Cough	0/26 (0%)	0	2/27 (7.4%)	3
Dyspnea	2/26 (7.7%)	7	0/27 (0%)	0
Sore Throat	6/26 (23.1%)	9	5/27 (18.5%)	5
Upper Respiratory Infection	2/26 (7.7%)	7	3/27 (11.1%)	5
Skin and subcutaneous tissue disorders
Alopecia	5/26 (19.2%)	11	6/27 (22.2%)	15
Dermatitis Radiation	0/26 (0%)	0	2/27 (7.4%)	4
Pruritis	2/26 (7.7%)	7	2/27 (7.4%)	3
Rash Masculo-Papular	7/26 (26.9%)	15	0/27 (0%)	0
Skin and Subcutaneous Tissue Disorders - Other	0/26 (0%)	0	2/27 (7.4%)	2
Vascular disorders
Thromboembolic Event	3/26 (11.5%)	6	0/27 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.