A Randomized Placebo-Controlled Trial of Armodafinil (Nuvigil) for Fatigue in Patients With Malignant Gliomas

• Sponsor: Eudocia Quant Lee, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT00766467
• Collaborator: Dartmouth-Hitchcock Medical Center (Other), University of California, San Diego (Other), Beth Israel Deaconess Medical Center (Other), Cephalon (Industry)
• Enrollment: 81
• Locations: 4
• Arms: 2
• Duration (Months): 69.9
• Patients Per Site: 20.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this research study is to determine if armodafinil is safe and effective in treating fatigue in patients with malignant gliomas undergoing treatment with radiotherapy plus temodar. Armodafinil is a wakefulness-promoting agent that has been FDA approved for the treatment of excessive daytime sleepiness for a variety of disorders. Armodafinil may also help to reduce radiation-induced fatigue in brain tumor patients.

Condition or Disease	Intervention/Treatment	Phase
Malignant Glioma	Drug: Armodafinil; Other: Placebo	Phase 2

Detailed Description

• Since no one knows for certain if armodafinil improves fatigue in brain tumor patients undergoing radiation therapy, participants will be randomized into one of two study groups. Half of the participants will receive armodafinil and the other half will receive pills with no medicine (placebo). Neither the participant or the study doctor will know what group they are in.

• Participants will be given a study medication-dosing calendar and will take either the study drug or placebo orally once a day for 8 weeks. The dose will be adjusted on days 8,22 or 43, depending upon the level of fatigue. Treatment will begin within 10 days from the radiation start date.

• Participants will be evaluated via documented clinician telephone call and self-administered questionnaires on days 1, 8, 22, 43 and 57.

Study Design

• Study Type: Interventional
• Actual Enrollment: 81 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Supportive Care
• Official Title: A Randomized Placebo-Controlled Trial of Armodafinil (Nuvigil) for Fatigue in Patients With Malignant Gliomas Undergoing Radiotherapy With or Without Standard Chemotherapy Treatment
• Study Start Date: Sep 1, 2008
• Actual Primary Completion Date: Jul 1, 2014
• Actual Study Completion Date: Jul 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 Armodafinil	Drug: Armodafinil; Taken orally once a day in the morning. Dose will change depending upon level of fatigue; Other Names: Nuvigil
Placebo Comparator: Group 2 Placebo	Other: Placebo; Placebo taken once a day in the morning

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Fatigue at Day 43 [43 days]

   The primary endpoint was the difference in the 42-day change (baseline vs. day 43) in Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F scale) between the 2 treatment groups (those patients randomized to receive armodafinil and those randomized to the placebo arm). FACIT-F is a well-validated QOL instrument widely used for the assessment of cancer-related fatigue in clinical trials.5 It consists of the 27-item FACT-G (which assesses QOL based on physical, social/family, emotional, and functional well-being) and the 13-item FACIT-F fatigue subscale (which assesses the impact of fatigue on daily activities). Each item is assessed on a 5-point scale (0 = not at all to 4 = very much). By scoring convention, after appropriate reversal scoring of 11 items, the FACIT-F fatigue subscale (FACIT-fatigue) score ranges from 0 to 52 (lower score indicating more fatigue). A score < 30 indicates severe fatigue.

Secondary Outcome Measures

1. Change From Baseline in Quality of Life at Days 22, 43 and 56 [baseline, day 22, day 43, and day 56]

   The effects of treatment on overall health-related quality of life quantified with the general Functional Assessment of Cancer Therapy survey (FACT-G) were measured at baseline, at day 22, at the end of radiation (day 43) and 2 weeks after completion of radiation (day 56). The FACT-G assesses quality of life based on physical, social/family, emotional, and functional well-being. Each item is assessed on a 5-point scale (0 = not at all to 4 = very much). The total FACT-G score can range from 0-108, with higher scores indicating a better quality of life.

2. Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment [56 days]

   To assess the side effect profile of armodafinil in patients with malignant gliomas undergoing radiotherapy with or without standard chemotherapy treatment.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• 18 years of age or older

• Histologically confirmed malignant glioma including anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma (WHO grade III/IV), glioblastoma multiforme (WHO grade IV) or gliosarcoma. Patients with a grade II astrocytoma, mixed oligo-astrocytoma or oligodendroglioma who are being treated with irradiation are also eligible

• Scheduled to receive irradiation to a total dose of 50-60 Gy. Patients receiving hyperfractionated radiotherapy are also eligible

• KPS of 70% or greater

• Electrolytes within normal institutional limits: BUN and Creatinine < 2.5 x ULN: AST, ALT, Bilirubin < 2.5 x ULN

• Able to swallow medication

Exclusion Criteria:

• History of recent cardiac arrhythmia or unstable angina

• Has taken a psychostimulant or a monoamine oxidase inhibitor on a regular basis within the past 30 days

• Clinically significant untreated sleep apnea

• A history of clinically significant cardiac disease, including a history of recent myocardial infarction, history of unstable angina, history of left ventricular hypertrophy, or a history of ischemic ECG changes, chest pain, arrhythmia, or other clinically significant manifestations of mitral valve prolapse in association with use of CNS stimulants (e.g. caffeine, amphetamines, methylphenidate)

• Uncontrolled hypertension, alcohol or drug abuse, severe headaches, glaucoma, narcolepsy, clinically significant untreated sleep apnea, psychotic disorder or Tourette's syndrome

• Patients taking warfarin for anticoagulation are eligible, but monitoring of prothrombin times is suggested as a precaution

• Hemoglobin level of less then 11 g/dl

• Laboratory evidence of hypothyroidism with an elevated TSH concentration in the blood greater than 5.0 mlU/L

• Current treatment or history of psychotic disorder, bipolar disorder, or anxiety disorder

• Patients with a score of > 28 on the Beck depression inventory consistent with severe depression

• Known hypersensitivity to armodafinil or related compounds

• Patients who have been receiving MAO inhibitors during the past 14 days

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSD San Diego	La Jolla	California	United States
2	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
3	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
4	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03766

Sponsors and Collaborators

• Eudocia Quant Lee, MD
• Dartmouth-Hitchcock Medical Center
• University of California, San Diego
• Beth Israel Deaconess Medical Center
• Cephalon

Investigators

• Principal Investigator: Eudocia Lee, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eudocia Quant Lee, MD, Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center
• ClinicalTrials.gov Identifier: NCT00766467
• Other Study ID Numbers: 07-341
• First Posted: Oct 6, 2008
• Last Update Posted: Jul 28, 2016
• Last Verified: Jun 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Eudocia Quant Lee, MD, Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center: armodafinil; Nuvigil; fatigue
• Additional relevant MeSH terms: Glioma; Fatigue; Modafinil

Study Results

Participant Flow

Recruitment Details	Study activated at Dana-Farber Cancer Institute in August 2008 and was eventually activated at Beth Israel Medical Center , Dartmouth Hitchcock Medical Center, and University of California San Diego. The study closed to new accrual as of April 2014 as the accrual was met.
Pre-assignment Detail	Randomization was performed by the Quality Assurance for Clinical Trials office at the Dana Farber Cancer Institute. Patients were randomized in a 1:1 basis to each treatment arm with no stratification.

Arm/Group Title	Armodafinil	Placebo
Arm/Group Description	Armodafinil: 150mg taken orally once a day in the morning.	Placebo: Taken orally once a day in the morning
Period Title: Overall Study
STARTED	42	39
Initiated Treatment	39	38
COMPLETED	31	31
NOT COMPLETED	11	8

Baseline Characteristics

Arm/Group Title	Armodafinil	Placebo	Total
Arm/Group Description	Armodafinil: Taken orally once a day in the morning.	Placebo: Taken orally once a day in the morning.	Total of all reporting groups
Overall Participants	42	39	81
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	56	54	55
Sex: Female, Male (Count of Participants)
Female	18 42.9%	18 46.2%	36 44.4%
Male	24 57.1%	21 53.8%	45 55.6%
Karnofsky Performance Status (KPS) (Units on a scale) [Median (Full Range) ]
Median (Full Range) [Units on a scale]	90	90	90
Glioma grade (units on a scale) [Number]
Grade 2	1	4	5
Grade 3	14	12	26
Grade 4	25	22	47
Grade not defined	2	1	3

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Fatigue at Day 43
Description	The primary endpoint was the difference in the 42-day change (baseline vs. day 43) in Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F scale) between the 2 treatment groups (those patients randomized to receive armodafinil and those randomized to the placebo arm). FACIT-F is a well-validated QOL instrument widely used for the assessment of cancer-related fatigue in clinical trials.5 It consists of the 27-item FACT-G (which assesses QOL based on physical, social/family, emotional, and functional well-being) and the 13-item FACIT-F fatigue subscale (which assesses the impact of fatigue on daily activities). Each item is assessed on a 5-point scale (0 = not at all to 4 = very much). By scoring convention, after appropriate reversal scoring of 11 items, the FACIT-F fatigue subscale (FACIT-fatigue) score ranges from 0 to 52 (lower score indicating more fatigue). A score < 30 indicates severe fatigue.
Time Frame	43 days

Outcome Measure Data

Analysis Population Description

Primary analysis included participants with complete or near complete baseline and day 43 data irrespective of the amount of treatment received.

Arm/Group Title	Armodafinil	Placebo
Arm/Group Description	Armodafinil: Taken orally once a day in the morning.	Placebo: Taken orally once a day in the morning.
Measure Participants	31	29
Median (80% Confidence Interval) [units on a scale]	-1	-3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Armodafinil, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Change From Baseline in Quality of Life at Days 22, 43 and 56
Description	The effects of treatment on overall health-related quality of life quantified with the general Functional Assessment of Cancer Therapy survey (FACT-G) were measured at baseline, at day 22, at the end of radiation (day 43) and 2 weeks after completion of radiation (day 56). The FACT-G assesses quality of life based on physical, social/family, emotional, and functional well-being. Each item is assessed on a 5-point scale (0 = not at all to 4 = very much). The total FACT-G score can range from 0-108, with higher scores indicating a better quality of life.
Time Frame	baseline, day 22, day 43, and day 56

Outcome Measure Data

Analysis Population Description

Analysis included participants with complete or near complete baseline and day 43 data irrespective of the amount of treatment received.

Arm/Group Title	Armodafinil	Placebo
Arm/Group Description	Armodafinil: Taken orally once a day in the morning.	Placebo: Taken orally once a day in the morning.
Measure Participants	31	29
FACIT-G (baseline vs day 22)	-1.76	-4.94
FACIT-G (baseline vs day 43)	2.50	-2.30
FACIT-G (baseline vs day 56)	1.83	-0.84

3. Secondary Outcome

Title	Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment
Description	To assess the side effect profile of armodafinil in patients with malignant gliomas undergoing radiotherapy with or without standard chemotherapy treatment.
Time Frame	56 days

Outcome Measure Data

Analysis Population Description

Grade 3 - 4 events at least possibly related to study treatment.

Arm/Group Title	Armodafinil	Placebo
Arm/Group Description	Armodafinil: Taken orally once a day in the morning.	Placebo: Taken orally once a day in the morning.
Measure Participants	42	39
Abdominal pain	1	0
Confusion	0	1
Dehydration	1	0
Diarrhea	1	1
Glaucoma	0	1
Hyperkalemia	1	0
Hypokalemia	1	0
Hypomagnesemia	1	0
Ileus	1	0
Insomnia	1	0
Mood alteration (agitation)	0	1
Obstruction, cecum	1	0
Rash	0	1
Seizure	1	0
Speech impairment	0	1

Adverse Events

Time Frame	Adverse events were collected on each participant from the time armodafinil/placebo was started up to Day 56 contact.
Adverse Event Reporting Description	Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.
Arm/Group Title	Armodafinil		Placebo
Arm/Group Description	Armodafinil: Taken orally once a day in the morning.		Placebo: Taken orally once a day in the morning.
All Cause Mortality
	Armodafinil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Armodafinil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/42 (7.1%)		5/39 (12.8%)
Blood and lymphatic system disorders
Platelets	0/42 (0%)	0	2/39 (5.1%)	2
Neutrophils	0/42 (0%)	0	1/39 (2.6%)	1
Gastrointestinal disorders
Obstruction, Cecum	1/42 (2.4%)	1	0/39 (0%)	0
Ileus	1/42 (2.4%)	1	0/39 (0%)	0
Abdominal pain	1/42 (2.4%)	1	0/39 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Disease progression NOS	0/42 (0%)	0	1/39 (2.6%)	1
Respiratory, thoracic and mediastinal disorders
Thrombosis/thrombus/embolism	1/42 (2.4%)	1	1/39 (2.6%)	1
Other (Not Including Serious) Adverse Events
	Armodafinil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/42 (85.7%)		33/39 (84.6%)
Blood and lymphatic system disorders
Hemoglobin	3/42 (7.1%)	4	3/39 (7.7%)	3
Leukocytes	1/42 (2.4%)	4	5/39 (12.8%)	11
Lymphopenia	1/42 (2.4%)	2	4/39 (10.3%)	9
Myelodysplasia	0/42 (0%)	0	1/39 (2.6%)	1
Neutrophils	2/42 (4.8%)	3	4/39 (10.3%)	9
Platelets	2/42 (4.8%)	4	4/39 (10.3%)	23
Hematologic-other	2/42 (4.8%)	5	5/39 (12.8%)	13
Lymphatics-other	0/42 (0%)	0	1/39 (2.6%)	2
Cardiac disorders
Heart block Wolff-Parkinson-White	0/42 (0%)	0	1/39 (2.6%)	1
Hypotension	1/42 (2.4%)	1	0/39 (0%)	0
Cardiac-other	2/42 (4.8%)	2	0/39 (0%)	0
Ear and labyrinth disorders
Hearing w/o audiogr not in monitor prg	1/42 (2.4%)	1	0/39 (0%)	0
Otitis, external ear (non-infectious)	1/42 (2.4%)	1	0/39 (0%)	0
Hearing-other	0/42 (0%)	0	1/39 (2.6%)	1
Endocrine disorders
Cushingnoid appearance	1/42 (2.4%)	1	2/39 (5.1%)	2
Eye disorders
Dry eye syndrome	0/42 (0%)	0	1/39 (2.6%)	1
Glaucoma	0/42 (0%)	0	1/39 (2.6%)	1
Vision-blurred	2/42 (4.8%)	2	2/39 (5.1%)	2
Ocular-other	1/42 (2.4%)	1	0/39 (0%)	0
Gastrointestinal disorders
Constipation	10/42 (23.8%)	10	7/39 (17.9%)	8
Teeth development	1/42 (2.4%)	1	0/39 (0%)	0
Diarrhea w/o prior colostomy	3/42 (7.1%)	3	2/39 (5.1%)	2
Dry mouth	3/42 (7.1%)	3	1/39 (2.6%)	1
Dysphagia	1/42 (2.4%)	1	0/39 (0%)	0
Gastritis	0/42 (0%)	0	1/39 (2.6%)	1
Dyspepsia	1/42 (2.4%)	1	0/39 (0%)	0
Hemorrhoids	1/42 (2.4%)	4	1/39 (2.6%)	1
Muco/stomatitis (symptom) oral cavity	0/42 (0%)	0	1/39 (2.6%)	1
Nausea	12/42 (28.6%)	17	11/39 (28.2%)	11
Taste disturbance	3/42 (7.1%)	3	2/39 (5.1%)	2
Vomiting	6/42 (14.3%)	6	3/39 (7.7%)	4
GI-other	1/42 (2.4%)	1	1/39 (2.6%)	2
Abdomen, pain	3/42 (7.1%)	4	0/39 (0%)	0
Dental/teeth/peridontal, pain	0/42 (0%)	0	1/39 (2.6%)	1
General disorders
Fatigue	17/42 (40.5%)	20	15/39 (38.5%)	20
Fever w/o neutropenia	2/42 (4.8%)	3	1/39 (2.6%)	1
Insomnia	13/42 (31%)	17	11/39 (28.2%)	15
Rigors/chills	0/42 (0%)	0	1/39 (2.6%)	1
Constitutional, other	3/42 (7.1%)	4	0/39 (0%)	0
Edema head and neck	1/42 (2.4%)	1	0/39 (0%)	0
Edema limb	1/42 (2.4%)	1	1/39 (2.6%)	1
Pain- other	2/42 (4.8%)	2	0/39 (0%)	0
Immune system disorders
Allergic Reaction	1/42 (2.4%)	1	0/39 (0%)	0
Infections and infestations
Infection w/ gr3-4 neut, oral cavity	1/42 (2.4%)	1	0/39 (0%)	0
Infection Gr0-2 neut, oral cavity	0/42 (0%)	0	1/39 (2.6%)	1
Infection Gr0-2 neut, paranasal	1/42 (2.4%)	1	0/39 (0%)	0
nfection Gr0-2 neut, urinary tract	0/42 (0%)	0	1/39 (2.6%)	2
nfection Gr0-2 neut, wound	1/42 (2.4%)	1	0/39 (0%)	0
Infection w/ unk ANC skin (cellulitis)	0/42 (0%)	0	1/39 (2.6%)	1
Infection-other	0/42 (0%)	0	1/39 (2.6%)	1
Investigations
Weight gain	0/42 (0%)	0	1/39 (2.6%)	1
Coagulation-other	0/42 (0%)	0	1/39 (2.6%)	2
ALT, SGPT	1/42 (2.4%)	1	4/39 (10.3%)	4
AST, SGOT	0/42 (0%)	0	1/39 (2.6%)	1
Hypercalcemia	0/42 (0%)	0	1/39 (2.6%)	1
Hyperglycemia	3/42 (7.1%)	3	2/39 (5.1%)	6
Hypoglycemia	1/42 (2.4%)	1	0/39 (0%)	0
Lipase	1/42 (2.4%)	1	0/39 (0%)	0
Hypomagnesemia	1/42 (2.4%)	1	0/39 (0%)	0
Hyperkalemia	1/42 (2.4%)	1	0/39 (0%)	0
Hypokalemia	1/42 (2.4%)	3	0/39 (0%)	0
Hyponatremia	1/42 (2.4%)	1	0/39 (0%)	0
Metabolic/Laboratory-other	1/42 (2.4%)	1	0/39 (0%)	0
Metabolism and nutrition disorders
Anorexia	6/42 (14.3%)	6	7/39 (17.9%)	7
Dehydration	1/42 (2.4%)	1	1/39 (2.6%)	1
Musculoskeletal and connective tissue disorders
Arthritis	1/42 (2.4%)	5	0/39 (0%)	0
Extremity-lower (gait/walking)	2/42 (4.8%)	2	1/39 (2.6%)	1
Nonneuropathic lower extr muscle weakness	0/42 (0%)	0	1/39 (2.6%)	1
Nonneuropathic upper extr muscle weakness	0/42 (0%)	0	1/39 (2.6%)	1
Nonneuropathic left-side muscle weakness	1/42 (2.4%)	1	0/39 (0%)	0
Nonneuropathic generalized weakness	1/42 (2.4%)	1	1/39 (2.6%)	1
Musculoskeletal/soft tissue-other	2/42 (4.8%)	3	0/39 (0%)	0
Back, pain	0/42 (0%)	0	1/39 (2.6%)	1
Dental/teeth/peridontal, pain	1/42 (2.4%)	1	4/39 (10.3%)	4
Joint, pain	2/42 (4.8%)	4	3/39 (7.7%)	3
Muscle, pain	1/42 (2.4%)	1	2/39 (5.1%)	5
Neck, pain	1/42 (2.4%)	2	2/39 (5.1%)	2
Nervous system disorders
CNS necrosis/cystic progression	0/42 (0%)	0	1/39 (2.6%)	1
Cognitive disturbance	2/42 (4.8%)	2	0/39 (0%)	0
Confusion	0/42 (0%)	0	2/39 (5.1%)	3
Dizziness	7/42 (16.7%)	9	6/39 (15.4%)	7
Memory impairment	0/42 (0%)	0	3/39 (7.7%)	3
Neuropathy CN II vision	1/42 (2.4%)	1	0/39 (0%)	0
Neuropathy CN V jaw / face-sensory	0/42 (0%)	0	1/39 (2.6%)	1
Neuropathy-motor	1/42 (2.4%)	1	3/39 (7.7%)	5
Neuropathy-sensory	1/42 (2.4%)	1	3/39 (7.7%)	3
Seizure	2/42 (4.8%)	3	1/39 (2.6%)	3
Speech impairment	2/42 (4.8%)	5	1/39 (2.6%)	2
Tremor	1/42 (2.4%)	1	0/39 (0%)	0
Neurologic-other	3/42 (7.1%)	4	7/39 (17.9%)	7
Headache	15/42 (35.7%)	23	11/39 (28.2%)	13
Psychiatric disorders
Agitation	1/42 (2.4%)	1	0/39 (0%)	0
Anxiety	12/42 (28.6%)	13	4/39 (10.3%)	5
Depression	2/42 (4.8%)	2	4/39 (10.3%)	4
Renal and urinary disorders
Urinary frequency/urgency	2/42 (4.8%)	2	3/39 (7.7%)	3
Renal - other	2/42 (4.8%)	2	0/39 (0%)	0
Respiratory, thoracic and mediastinal disorders
Nose, hemorrhage	0/42 (0%)	0	1/39 (2.6%)	1
Cough	1/42 (2.4%)	1	0/39 (0%)	0
Dyspnea	0/42 (0%)	0	1/39 (2.6%)	1
Thrombosis/thrombus/embolism	3/42 (7.1%)	3	1/39 (2.6%)	1
Skin and subcutaneous tissue disorders
Dry skin	1/42 (2.4%)	1	0/39 (0%)	0
Alopecia	0/42 (0%)	0	2/39 (5.1%)	2
Hyperpigmentation	0/42 (0%)	0	1/39 (2.6%)	1
Pruritus/itching	2/42 (4.8%)	3	2/39 (5.1%)	2
Rash/desquamation	3/42 (7.1%)	3	5/39 (12.8%)	5
Rash: acne/acneiform	0/42 (0%)	0	1/39 (2.6%)	1
Radiation dermatitis	3/42 (7.1%)	3	0/39 (0%)	0
Skin-other	4/42 (9.5%)	7	2/39 (5.1%)	2
Vascular disorders
Hot flashes	0/42 (0%)	0	1/39 (2.6%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.