One-Year Safety and Tolerability Study of Azilsartan Medoxomil in Participants With Essential Hypertension

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00695955
• Collaborator: (none)
• Enrollment: 669
• Locations: 41
• Arm: 1
• Duration (Months): 35
• Patients Per Site: 16.3
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This purpose of this study is to evaluate the long-term safety and tolerability of azilsartan medoxomil in individuals with essential hypertension.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Azilsartan medoxomil with or without add-on chlorthalidone; Drug: Azilsartan medoxomil with or without add-on hydrochlorothiazide	Phase 3

Detailed Description

Hypertension affects approximately 50 million individuals in the United States. As the population ages, the prevalence of hypertension will continue to increase if broad and effective preventive measures are not implemented. According to the World Health Organization, hypertension is the most common attributable cause of preventable death in developed nations, as uncontrolled hypertension greatly increases the risk of cardiovascular disease, cerebrovascular disease, and renal failure. Despite the availability of antihypertensive treatments, hypertension remains inadequately controlled; only about one-third of patients continue to maintain control successfully.

Takeda Global Research and Development is developing TAK-491 (azilsartan medoxomil) for the treatment of essential hypertension. This study is being conducted to demonstrate the long-term safety and tolerability of azilsartan medoxomil in individuals with essential hypertension.

Study participation is anticipated to be approximately 1 year and 1.5 months, and participants will be required to return to the clinic for 10 study visits.

Study Design

• Study Type: Interventional
• Actual Enrollment: 669 participants
• Allocation: Non-Randomized
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A One-Year Phase 3, Open-Label Study to Evaluate the Safety and Tolerability of TAK-491 in Subjects With Essential Hypertension
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Azilsartan Medoxomil

Drug: Azilsartan medoxomil with or without add-on chlorthalidone; Azilsartan medoxomil 40 mg, tablets, orally, once daily for four weeks; increased to azilsartan medoxomil 80 mg, tablets, orally, once daily for remainder of 56-week treatment period, if tolerated. Additional antihypertensive medications added, beginning with chlorthalidone 25 mg, once-daily, if target blood pressure not achieved.; Other Names: TAK-491 Edarbi ; Drug: Azilsartan medoxomil with or without add-on hydrochlorothiazide; Azilsartan medoxomil 40 mg, tablets, orally, once daily for four weeks; increased to azilsartan medoxomil 80 mg, tablets, orally, once daily for remainder of 56-week treatment period, if tolerated. Additional antihypertensive medications added, beginning with hydrochlorothiazide 12.5 to 25 mg, once-daily, if target blood pressure not achieved.; Other Names: TAK-491 Edarbi

Outcome Measures

Primary Outcome Measures

1. Number of Participants Reporting One or More Treatment-emergent Adverse Events From Day 1 Through End of the Study - Cohort 1. [56 weeks.]

   Treatment-emergent adverse events are defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug.

2. Number of Participants Reporting One or More Treatment-emergent Adverse Events From Day 1 Through End of the Study - Cohort 2. [56 weeks.]

   Treatment-emergent adverse events are defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug.

Secondary Outcome Measures

1. Change From Baseline in Sitting Clinic Systolic Blood Pressure - Cohort 1. [52 weeks]

   The change between sitting clinic systolic blood pressure measured at each week assessed relative to the baseline measurement. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.

2. Change From Baseline in Sitting Clinic Systolic Blood Pressure - Cohort 2 [52 weeks]

   The change between sitting clinic systolic blood pressure measured at each week assessed relative to the baseline measurement. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.

3. Change From Baseline in Sitting Clinic Diastolic Blood Pressure - Cohort 1. [52 weeks.]

   The change between sitting clinic diastolic blood pressure measured at each week assessed relative to the baseline measurement. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.

4. Change From Baseline in Sitting Clinic Diastolic Blood Pressure - Cohort 2. [52 weeks.]

   The change between sitting clinic diastolic blood pressure measured at each week assessed relative to the baseline measurement. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.

Eligibility Criteria

Criteria

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

Inclusion Criteria

1. Diastolic blood pressure greater than or equal to 95 mm Hg and less than or equal to 119 mm Hg. For diabetic subjects and subjects with chronic kidney disease, diastolic blood pressure must be greater than or equal to 85 mm Hg and less than or equal to109 mm Hg).

2. Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating.

3. Clinical laboratory evaluations within the reference range for or deemed not clinically significant by the investigator.

Exclusion Criteria

1. Systolic blood pressure greater than 185 mm Hg.

2. Expected to take angiotensin II receptor blockers other than the study drug.

3. Taking more than 2 antihypertensive agents.

4. Hypersensitive to angiotensin II receptor blockers, thiazide-type diuretics or sulfonamide-derived compounds.

5. Recent history of major cardiovascular event.

6. History of moderate to severe heart failure or hypertensive encephalopathy.

7. Clinically significant cardiac conduction defects.

8. Secondary hypertension of any etiology.

9. Known or suspected unilateral or bilateral renal artery stenosis.

10. Severe renal dysfunction or disease.

11. History of drug abuse or a history of alcohol abuse within the past 2 years.

12. Previous history of cancer that has not been in remission for at least 5 years prior to the first dose of study drug..

13. Uncontrolled diabetes mellitus.

14. Alanine aminotransferase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice.

15. Serum potassium level of greater than the upper limit of normal.

16. Currently is participating in another investigational study or has participated in an investigational study within 30 days prior to enrollment.

17. Any other serious disease or condition.

18. Randomized in a previous azilsartan medoxomil study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Ozark	Alabama	United States
2		Tallassee	Alabama	United States
3		Long Beach	California	United States
4		Santa Rosa	California	United States
5		Spring Valley	California	United States
6		Colorado Springs	Colorado	United States
7		Trumbull	Connecticut	United States
8		Waterbury	Connecticut	United States
9		Fort Lauderdale	Florida	United States
10		Hollywood	Florida	United States
11		Jacksonville	Florida	United States
12		Miami	Florida	United States
13		Pembroke Pines	Florida	United States
14		Pinellas Park	Florida	United States
15		Atlanta	Georgia	United States
16		Augusta	Georgia	United States
17		Brooklyn Center	Minnesota	United States
18		Olive Branch	Mississippi	United States
19		Rochester	New York	United States
20		Charlotte	North Carolina	United States
21		Raleigh	North Carolina	United States
22		Salisbury	North Carolina	United States
23		Winston-Salem	North Carolina	United States
24		Akron	Ohio	United States
25		Cincinnati	Ohio	United States
26		Mogadore	Ohio	United States
27		Springdale	Ohio	United States
28		Oklahoma City	Oklahoma	United States
29		Philadelphia	Pennsylvania	United States
30		Anderson	South Carolina	United States
31		Mt. Pleasant	South Carolina	United States
32		Simpsonville	South Carolina	United States
33		Bristol	Tennessee	United States
34		Nashville	Tennessee	United States
35		Arlington	Texas	United States
36		Austin	Texas	United States
37		North Richland Hills	Texas	United States
38		Salt Lake City	Utah	United States
39		Norfolk	Virginia	United States
40		San Bernardo	Santiago	Chile
41		Tijuana	BC	Mexico

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Executive Medical Director Clinical Science, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00695955
• Other Study ID Numbers: 01-05-TL-491-006; U1111-1113-8874
• First Posted: Jun 12, 2008
• Last Update Posted: Apr 19, 2011
• Last Verified: Mar 1, 2011

• Keywords provided by , ,: Essential Hypertension; Cardiovascular Disease; High Blood Pressure; Drug Therapy
• Additional relevant MeSH terms: Hypertension; Essential Hypertension; Hydrochlorothiazide; Chlorthalidone; Azilsartan medoxomil

Study Results

Participant Flow

Recruitment Details	Participants enrolled at 39 investigative sites in Chile, Mexico and the United States from 22 June 2007 to 30 April 2010.
Pre-assignment Detail	Participants with essential hypertension were enrolled in a once-daily (QD) treatment group.

Arm/Group Title	Azilsartan Medoxomil
Arm/Group Description	Cohort 1: Azilsartan medoxomil 40 mg, tablets, orally, once daily for four weeks; increased to azilsartan medoxomil 80 mg, tablets, orally, once daily for remainder of 56-week treatment period, if tolerated. Additional antihypertensive medications added, beginning with chlorthalidone 25 mg, once-daily, if target blood pressure not achieved. Cohort 2: Azilsartan medoxomil 40 mg, tablets, orally, once daily for four weeks; increased to azilsartan medoxomil 80 mg, tablets, orally, once daily for remainder of 56-week treatment period, if tolerated. Additional antihypertensive medications added, beginning with hydrochlorothiazide 12.5 to 25 mg, once-daily, if target blood pressure not achieved.
Period Title: Cohort 1
STARTED	362
COMPLETED	260
NOT COMPLETED	102
Period Title: Cohort 1
STARTED	307
COMPLETED	203
NOT COMPLETED	104

Baseline Characteristics

Arm/Group Title	Azilsartan Medoxomil
Arm/Group Description	Cohort 1: Azilsartan medoxomil 40 mg, tablets, orally, once daily for four weeks; increased to azilsartan medoxomil 80 mg, tablets, orally, once daily for remainder of 56-week treatment period, if tolerated. Additional antihypertensive medications added, beginning with chlorthalidone 25 mg, once-daily, if target blood pressure not achieved. Cohort 2: Azilsartan medoxomil 40 mg, tablets, orally, once daily for four weeks; increased to azilsartan medoxomil 80 mg, tablets, orally, once daily for remainder of 56-week treatment period, if tolerated. Additional antihypertensive medications added, beginning with hydrochlorothiazide 12.5 to 25 mg, once-daily, if target blood pressure not achieved.
Overall Participants	669
Age, Customized (participants) [Number]
<45 years (Cohort 1)	81 12.1%
Between 45 and 64 years (Cohort 1)	233 34.8%
≥65 years (Cohort 1)	48 7.2%
<45 years (Cohort 2)	90 13.5%
Between 45 and 64 years (Cohort 2)	193 28.8%
≥65 years (Cohort 2)	24 3.6%
Sex/Gender, Customized (participants) [Number]
Female (Cohort 1)	173 25.9%
Male (Cohort 1)	189 28.3%
Female (Cohort 2)	144 21.5%
Male (Cohort 2)	163 24.4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Reporting One or More Treatment-emergent Adverse Events From Day 1 Through End of the Study - Cohort 1.
Description	Treatment-emergent adverse events are defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug.
Time Frame	56 weeks.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Cohort 1
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once daily for four weeks; increased to azilsartan medoxomil 80 mg, tablets, orally, once daily for remainder of 56-week treatment period, if tolerated. Additional antihypertensive medications added, beginning with chlorthalidone 25 mg, once-daily, if target blood pressure not achieved.
Measure Participants	362
Number of Participants	267 39.9%
Percentage of Participants	73.8 11%

2. Primary Outcome

Title	Number of Participants Reporting One or More Treatment-emergent Adverse Events From Day 1 Through End of the Study - Cohort 2.
Description	Treatment-emergent adverse events are defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug.
Time Frame	56 weeks.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Cohort 2
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once daily for four weeks; increased to azilsartan medoxomil 80 mg, tablets, orally, once daily for remainder of 56-week treatment period, if tolerated. Additional antihypertensive medications added, beginning with hydrochlorothiazide 12.5 to 25 mg, once-daily, if target blood pressure not achieved.
Measure Participants	307
Number of Participants	241 36%
Percentage of Participants	78.5 11.7%

3. Secondary Outcome

Title	Change From Baseline in Sitting Clinic Systolic Blood Pressure - Cohort 1.
Description	The change between sitting clinic systolic blood pressure measured at each week assessed relative to the baseline measurement. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Cohort 1
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once daily for four weeks; increased to azilsartan medoxomil 80 mg, tablets, orally, once daily for remainder of 56-week treatment period, if tolerated. Additional antihypertensive medications added, beginning with chlorthalidone 25 mg, once-daily, if target blood pressure not achieved.
Measure Participants	362
Week 4	-10.1 (15.21)
Week 8	-13.1 (16.72)
Week 12	-21.5 (15.80)
Week 16	-25.4 (15.09)
Week 26	-26.3 (15.97)
Week 36	-27.3 (16.63)
Week 46	-28.1 (17.21)
Week 56	-25.2 (18.05)
Final Visit	-22.1 (18.64)

4. Secondary Outcome

Title	Change From Baseline in Sitting Clinic Systolic Blood Pressure - Cohort 2
Description	The change between sitting clinic systolic blood pressure measured at each week assessed relative to the baseline measurement. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Cohort 2
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once daily for four weeks; increased to azilsartan medoxomil 80 mg, tablets, orally, once daily for remainder of 56-week treatment period, if tolerated. Additional antihypertensive medications added, beginning with hydrochlorothiazide 12.5 to 25 mg, once-daily, if target blood pressure not achieved.
Measure Participants	307
Week 4	-14.4 (13.57)
Week 8	-17.5 (15.07)
Week 12	-23.8 (15.97)
Week 16	-26.2 (15.65)
Week 26	-24.8 (15.25)
Week 36	-22.5 (14.89)
Week 46	-23.8 (15.35)
Week 56	-24.2 (15.96)
Final Visit	-22.7 (17.14)

5. Secondary Outcome

Title	Change From Baseline in Sitting Clinic Diastolic Blood Pressure - Cohort 1.
Description	The change between sitting clinic diastolic blood pressure measured at each week assessed relative to the baseline measurement. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.
Time Frame	52 weeks.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Cohort 1
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once daily for four weeks; increased to azilsartan medoxomil 80 mg, tablets, orally, once daily for remainder of 56-week treatment period, if tolerated. Additional antihypertensive medications added, beginning with chlorthalidone 25 mg, once-daily, if target blood pressure not achieved.
Measure Participants	362
Week 4	-8.9 (8.73)
Week 8	-11.0 (9.97)
Week 12	-15.9 (9.12)
Week 16	-18.7 (9.06)
Week 26	-18.6 (9.15)
Week 36	-19.9 (9.13)
Week 46	-19.8 (9.67)
Week 56	-18.4 (9.52)
Final Visit	-16.5 (10.23)

6. Secondary Outcome

Title	Change From Baseline in Sitting Clinic Diastolic Blood Pressure - Cohort 2.
Description	The change between sitting clinic diastolic blood pressure measured at each week assessed relative to the baseline measurement. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.
Time Frame	52 weeks.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Cohort 2
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once daily for four weeks; increased to azilsartan medoxomil 80 mg, tablets, orally, once daily for remainder of 56-week treatment period, if tolerated. Additional antihypertensive medications added, beginning with hydrochlorothiazide 12.5 to 25 mg, once-daily, if target blood pressure not achieved.
Measure Participants	307
Week 4	-10.6 (9.23)
Week 8	-12.3 (9.05)
Week 12	-16.8 (9.48)
Week 16	-18.2 (10.28)
Week 26	-17.7 (10.95)
Week 36	-16.2 (9.08)
Week 46	-17.2 (9.57)
Week 56	-17.9 (10.85)
Final Visit	-16.2 (11.05)

Adverse Events

Time Frame	Treatment-emergent adverse events (TEAEs) defined as any AEs, regardless of relationship to study drug, that occur after the first dose of study drug and within 14 days after last dose, or if an SAE, within 30 days after the last dose of study drug.
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title	Cohort 1		Cohort 2
Arm/Group Description	Azilsartan medoxomil 40 mg, tablets, orally, once daily for four weeks; increased to azilsartan medoxomil 80 mg, tablets, orally, once daily for remainder of 56-week treatment period, if tolerated. Additional antihypertensive medications added, beginning with chlorthalidone 25 mg, once-daily, if target blood pressure not achieved.		Azilsartan medoxomil 40 mg, tablets, orally, once daily for four weeks; increased to azilsartan medoxomil 80 mg, tablets, orally, once daily for remainder of 56-week treatment period, if tolerated. Additional antihypertensive medications added, beginning with hydrochlorothiazide 12.5 to 25 mg, once-daily, if target blood pressure not achieved.
All Cause Mortality
	Cohort 1		Cohort 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Cohort 1		Cohort 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/362 (8.3%)		22/307 (7.2%)
Blood and lymphatic system disorders
Anaemia	0/362 (0%)		1/307 (0.3%)
Cardiac disorders
Coronary artery disease	2/362 (0.6%)		0/307 (0%)
Acute myocardial infarction	1/362 (0.3%)		0/307 (0%)
Angina pectoris	0/362 (0%)		1/307 (0.3%)
Atrial flutter	0/362 (0%)		1/307 (0.3%)
Atrioventricular block	0/362 (0%)		1/307 (0.3%)
Myocardial infarction	0/362 (0%)		1/307 (0.3%)
Tachycardia	0/362 (0%)		1/307 (0.3%)
Eye disorders
Maculopathy	1/362 (0.3%)		0/307 (0%)
Gastrointestinal disorders
Small intestinal obstruction	1/362 (0.3%)		1/307 (0.3%)
Abdominal pain upper	1/362 (0.3%)		0/307 (0%)
Appendiceal mucocoele	1/362 (0.3%)		0/307 (0%)
Appendicitis perforated	1/362 (0.3%)		0/307 (0%)
Diarrhoea	1/362 (0.3%)		0/307 (0%)
Dyspepsia	1/362 (0.3%)		0/307 (0%)
Gastritis	0/362 (0%)		1/307 (0.3%)
Gastrooesophageal reflux disease	0/362 (0%)		1/307 (0.3%)
Oesophagitis	1/362 (0.3%)		0/307 (0%)
Retroperitoneal haemorrhage	0/362 (0%)		1/307 (0.3%)
Vomiting	1/362 (0.3%)		0/307 (0%)
General disorders
Chest pain	1/362 (0.3%)		2/307 (0.7%)
Hepatobiliary disorders
Cholecystitis	1/362 (0.3%)		0/307 (0%)
Infections and infestations
Acquired immunodeficiency syndrome	1/362 (0.3%)		0/307 (0%)
Cellulitis	0/362 (0%)		1/307 (0.3%)
Diverticulitis	1/362 (0.3%)		0/307 (0%)
Gastroenteritis viral	0/362 (0%)		1/307 (0.3%)
Septic shock	1/362 (0.3%)		0/307 (0%)
Staphylococcal infection	1/362 (0.3%)		0/307 (0%)
Subcutaneous abscess	0/362 (0%)		1/307 (0.3%)
Urinary tract infection	1/362 (0.3%)		0/307 (0%)
Viral infection	1/362 (0.3%)		0/307 (0%)
Injury, poisoning and procedural complications
Road traffic accident	1/362 (0.3%)		1/307 (0.3%)
Alcohol poisoning	0/362 (0%)		1/307 (0.3%)
Splenic haematoma	0/362 (0%)		1/307 (0.3%)
Thermal burn	1/362 (0.3%)		0/307 (0%)
Tibia fracture	1/362 (0.3%)		0/307 (0%)
Investigations
Blood creatinine increased	1/362 (0.3%)		0/307 (0%)
Metabolism and nutrition disorders
Dehydration	1/362 (0.3%)		0/307 (0%)
Diabetic ketoacidosis	1/362 (0.3%)		0/307 (0%)
Hypokalaemia	1/362 (0.3%)		0/307 (0%)
Hypovolaemia	0/362 (0%)		1/307 (0.3%)
Musculoskeletal and connective tissue disorders
Compartment syndrome	1/362 (0.3%)		0/307 (0%)
Pain in extremity	0/362 (0%)		1/307 (0.3%)
Spinal osteoarthritis	1/362 (0.3%)		0/307 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/362 (0.3%)		0/307 (0%)
Prostate cancer	1/362 (0.3%)		0/307 (0%)
Thyroid cancer	1/362 (0.3%)		0/307 (0%)
Nervous system disorders
Syncope vasovagal	2/362 (0.6%)		0/307 (0%)
Cerebrovascular accident	1/362 (0.3%)		0/307 (0%)
Syncope	1/362 (0.3%)		0/307 (0%)
Transient ischaemic attack	0/362 (0%)		1/307 (0.3%)
Psychiatric disorders
Completed suicide	1/362 (0.3%)		0/307 (0%)
Depression	0/362 (0%)		1/307 (0.3%)
Post-traumatic stress disorder	0/362 (0%)		1/307 (0.3%)
Psychotic disorder	0/362 (0%)		1/307 (0.3%)
Renal and urinary disorders
Renal impairment	1/362 (0.3%)		0/307 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/362 (0.3%)		1/307 (0.3%)
Pulmonary embolism	0/362 (0%)		2/307 (0.7%)
Skin and subcutaneous tissue disorders
Stevens-Johnson syndrome	0/362 (0%)		1/307 (0.3%)
Vascular disorders
Hypotension	1/362 (0.3%)		1/307 (0.3%)
Deep vein thrombosis	0/362 (0%)		1/307 (0.3%)
Malignant hypertension	0/362 (0%)		1/307 (0.3%)
Other (Not Including Serious) Adverse Events
	Cohort 1		Cohort 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	134/362 (37%)		106/307 (34.5%)
General disorders
Fatigue	32/362 (8.8%)		16/307 (5.2%)
Infections and infestations
Upper respiratory tract infection	25/362 (6.9%)		20/307 (6.5%)
Urinary tract infection	26/362 (7.2%)		11/307 (3.6%)
Nervous system disorders
Dizziness	52/362 (14.4%)		44/307 (14.3%)
Headache	38/362 (10.5%)		28/307 (9.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

No publication related to study results will be published prior to publication of a multi-center report submitted for publication within 18 months after conclusion or termination of a study at all study sites. Results publications will be submitted to sponsor for review 60 days in advance of publication. Sponsor can require removal of confidential information unrelated to study results. Sponsor can embargo a proposed publication for another 60 days to preserve intellectual property.