Study to Evaluate Tezepelumab on Airway Inflammation in Adults With Uncontrolled Asthma (CASCADE)

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03688074
• Collaborator: Amgen (Industry)
• Enrollment: 116
• Locations: 28
• Arms: 2
• Actual Duration (Months): 24.5
• Patients Per Site: 4.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

A phase 2, multicentre, randomized, double-blind, placebo-controlled, parallel group study to evaluate the effect of tezepelumab on airway inflammation in adults with inadequately controlled asthma.

Condition or Disease	Intervention/Treatment	Phase
Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases	Biological: Tezepelumab; Other: Placebo	Phase 2

Detailed Description

This is a multicentre, randomized, double-blind, placebo-controlled, parallel group study to evaluate the effect of tezepelumab on airway inflammation in adults with inadequately controlled moderate-to-severe asthma, taking inhaled corticosteroids and at least one additional asthma controller. Approximately 110 subjects will be randomized globally. Subjects will receive tezepelumab, or placebo, administered via subcutaneous injection at the study site, over a 28-week treatment period. Although, due to the Covid-19 pandemic this may be an extended time frame for some subject visits. The study also includes a post-treatment follow-up period of 12 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 116 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Subjects will be randomized in a 1:1 ratio to either tezepelumab or matching placebo both administered subcutaneously.Subjects will be randomized in a 1:1 ratio to either tezepelumab or matching placebo both administered subcutaneously.
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Double-blind
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Double-blind, Parallel Group, Placebo Controlled Study to Evaluate the Effect of Tezepelumab on Airway Inflammation in Adults With Inadequately Controlled Asthma on Inhaled Corticosteroids and at Least One Additional Asthma Controller (CASCADE)
• Actual Study Start Date: Nov 2, 2018
• Actual Primary Completion Date: Nov 16, 2020
• Actual Study Completion Date: Nov 16, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tezepelumab Tezepelumab subcutaneous injection	Biological: Tezepelumab; Tezepelumab subcutaneous injection
Placebo Comparator: Placebo Placebo subcutaneous injection	Other: Placebo; Placebo subcutaneous injection

Outcome Measures

Primary Outcome Measures

1. Airway Submucosal Inflammatory Cells Ratio Change From Baseline to EOT. [First dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).]

   The change from baseline to end of treatment (EOT) expressed as a ratio i.e. (EOT/baseline) in numbers of each of the airway submucosal inflammatory cells, determined by microscopic evaluation of bronchoscopic biopsies.

Secondary Outcome Measures

1. Reticular Basement Membrane (RBM) Thickness Ratio Change From Baseline to EOT. [First dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).]

   The change from baseline to EOT expressed as a ratio i.e. (EOT/baseline) in RBM thickness, determined by microscopic evaluation of bronchoscopic biopsies.

2. Percent (%) Airway Epithelial Integrity Ratio Change From Baseline to EOT. [First dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).]

   The change from baseline to EOT expressed as a ratio i.e. (EOT/baseline) in % airway epithelial, determined by microscopic evaluation of bronchoscopic biopsies.

Eligibility Criteria

Criteria

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

Principal Inclusion Criteria:

• Subject must be 18 to 75 years of age.

• Documented physician-diagnosed asthma for at least 12 months.

• Subjects who have received a physician- prescribed asthma controller medication with medium or high dose ICS for at least 12 months; must be stable for at least 3 months prior to screening visit.

• At least one additional maintenance asthma controller medication is required according to standard practice of care and must be documented for at least 3 months.

• At enrolment, the subject must have a predicted normal value for the morning pre-bronchodilator FEV1>50% and more than 1L.

• Evidence of asthma as documented by reversibility of FEV1 ≥12% and ≥200 mL in the previous 12 months prior to screening, or during the screening period prior to randomization.

• ACQ-6 score ≥ 1.5 during the screening period prior to randomization.

Principal Exclusion Criteria:

• Any clinically important pulmonary disease other than asthma.

• History of cancer.

• Hospitalization or required OCS for asthma exacerbation within 6 weeks of enrolment or

3 exacerbations requiring OCS or hospitalization in the year prior to visit 1 or who had been intubated or admitted to ICU for asthma exacerbation in the year prior to enrolment.

• History of a clinically significant infection, including upper (URTI) or lower respiratory tract infection (LRTI), requiring treatment with antibiotics or antiviral medications finalized <2 weeks before visit 1 or during the run-in period.

• Current smokers or subjects with smoking history ≥10 pack-yrs, including e-cigarettes. Former smokers with a smoking history of <10 pack-yrs must have stopped for at least 6 months prior to visit 1, including e-cigarette use.

• History of chronic alcohol or drug abuse within 12 months prior to visit 1.

• Tuberculosis requiring treatment within 12 months prior to visit 1.

• History of known immunodeficiency disorder including a positive HIV test at visit 1, or the subject is taking antiretroviral medications as determined by medical history and/or subject's verbal report.

• History of anaphylaxis or documented immune complex disease (type III hypersensitivity reactions) following any biologic therapy Subject randomized in a previous Tezepelumab study or in a current study with another investigational product.

• Pregnant, breastfeeding or lactating women.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Denver	Colorado	United States	80206
2	Research Site	New Haven	Connecticut	United States	06510
3	Research Site	Boston	Massachusetts	United States	02115
4	Research Site	Pittsburgh	Pennsylvania	United States	15213
5	Research Site	Galveston	Texas	United States	77555
6	Research Site	Calgary	Alberta	Canada	T2N 4Z6
7	Research Site	Vancouver	British Columbia	Canada	V5Z 1M9
8	Research Site	Hamilton	Ontario	Canada	L8N 3Z5
9	Research Site	Ottawa	Ontario	Canada	K1H 8L6
10	Research Site	Montreal	Quebec	Canada	H4A 3J1
11	Research Site	Quebec		Canada	G1V 4G5
12	Research Site	Aarhus N		Denmark	8200
13	Research Site	Hvidovre		Denmark	2650
14	Research Site	København NV		Denmark	2400
15	Research Site	Naestved		Denmark	4700
16	Research Site	Odense C		Denmark	5000
17	Research Site	Vejle		Denmark	7100
18	Research Site	Ålborg		Denmark	9000
19	Research Site	Frankfurt/Main		Germany	60389
20	Research Site	Frankfurt		Germany	60596
21	Research Site	Grosshansdorf		Germany	22927
22	Research Site	Landsberg		Germany	86899
23	Research Site	Cambridge		United Kingdom	CB2 0QQ
24	Research Site	Headington		United Kingdom	OX3 9DU
25	Research Site	Leicester		United Kingdom	LE3 9QP
26	Research Site	London		United Kingdom	W1G 8HU
27	Research Site	Nottingham		United Kingdom	NG5 1PB
28	Research Site	Wythenshawe		United Kingdom	M23 9QZ

Sponsors and Collaborators

• AstraZeneca
• Amgen

Investigators

• Principal Investigator: Chris Brightling, University of Leicester, United Kingdom

Study Documents (Full-Text)

• Study Protocol - Apr 30, 2020
• Statistical Analysis Plan - Nov 15, 2020

More Information

Additional Information:

• Statistical Analysis Plan (SAP)
• CSP

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT03688074
• Other Study ID Numbers: D5180C00013
• First Posted: Sep 28, 2018
• Last Update Posted: Feb 21, 2022
• Last Verified: Feb 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by AstraZeneca: Asthma; Uncontrolled asthma; Severe uncontrolled asthma
• Additional relevant MeSH terms: Asthma; Lung Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Bronchial Diseases; Respiratory Hypersensitivity; Hypersensitivity; Immune System Diseases; Hypersensitivity, Immediate; Inflammation

Study Results

Participant Flow

Recruitment Details	116 subjects randomized to Tezepelumab 210 mg Q4W or Placebo in 1:1 treatment allocation. All randomized subjects were treated.
Pre-assignment Detail	The study randomized subjects across the spectrum of T2 status. Randomization was stratified by screening blood eosinophil level (<150 , 150 - <300, >=300 cells/µL).

Arm/Group Title	Teze 210 mg Q4W	Placebo
Arm/Group Description	Tezepelumab subcutaneous injection	Placebo subcutaneous injection
Period Title: Overall Study
STARTED	59	57
COMPLETED	58	56
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Teze 210 mg Q4W	Placebo	Total
Arm/Group Description	Tezepelumab subcutaneous injection	Placebo subcutaneous injection	Total of all reporting groups
Overall Participants	59	57	116
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	51 86.4%	49 86%	100 86.2%
>=65 years	8 13.6%	8 14%	16 13.8%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	50.4 (12.7)	50.4 (13.9)	50.4 (13.2)
Sex: Female, Male (Count of Participants)
Female	39 66.1%	26 45.6%	65 56%
Male	20 33.9%	31 54.4%	51 44%
Race/Ethnicity, Customized (Count of Participants)
White	54 91.5%	55 96.5%	109 94%
Black or African American	2 3.4%	1 1.8%	3 2.6%
Asian	2 3.4%	1 1.8%	3 2.6%
Other (includes Native Hawaiian or Other Pacific Islander and American Indian or Alaska Native)	1 1.7%	0 0%	1 0.9%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	59 100%	57 100%	116 100%

Outcome Measures

1. Primary Outcome

Title	Airway Submucosal Inflammatory Cells Ratio Change From Baseline to EOT.
Description	The change from baseline to end of treatment (EOT) expressed as a ratio i.e. (EOT/baseline) in numbers of each of the airway submucosal inflammatory cells, determined by microscopic evaluation of bronchoscopic biopsies.
Time Frame	First dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).

Outcome Measure Data

Analysis Population Description

Number of Participants Analyzed are all subjects randomized to study treatment who completed at least 20 weeks of study treatment and had an EOT visit not greater than 8 weeks after date of last dose of IP. In order to be included in analysis, the participants also had to have a non-missing baseline as well as a non-missing EOT assessment for the respective variable.

Arm/Group Title	Teze 210 mg Q4W	Placebo
Arm/Group Description	Tezepelumab subcutaneous injection	Placebo subcutaneous injection
Measure Participants	54	56
Eosinophils	0.11	0.75
Neutrophils	1.11	0.81
T cells CD3+	0.91	0.81
T cells CD4+	0.96	0.81
Mast cells Tryptase+	0.84	1.01
Mast cells Chymase+	1.07	0.90

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Teze 210 mg Q4W, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Nominal p-values were reported. No adjustment of multiplicity was performed.
	Method	ANCOVA
	Comments	Model includes treatment+log transformed baseline value+stratification factor (screening eos count [<150, 150-<300, >=300 cells/uL])
Method of Estimation	Estimation Parameter	Ratio of Geometric LSMeans
	Estimated Value	0.15
	Confidence Interval	(2-Sided) 90%; 0.06 to 0.35
	Parameter Dispersion	Type: Value:
	Estimation Comments	Parameter : Eosinophils (cells/mm^2)
Other Statistical Analysis		95% CI (0.05, 0.41)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Teze 210 mg Q4W, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.106
	Comments	Nominal p-values were reported. No adjustment of multiplicity was performed.
	Method	ANCOVA
	Comments	Model includes treatment+log transformed baseline value+stratification factor (screening eos count [<150, 150-<300, >=300 cells/uL])
Method of Estimation	Estimation Parameter	Ratio of Geometric LSMeans
	Estimated Value	1.36
	Confidence Interval	(2-Sided) 90%; 0.99 to 1.86
	Parameter Dispersion	Type: Value:
	Estimation Comments	Parameter: Neutrophils (cells/mm^2)
Other Statistical Analysis		95% CI (0.94, 1.97)

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Teze 210 mg Q4W, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.389
	Comments	Nominal p-values were reported. No adjustment of multiplicity was performed.
	Method	ANCOVA
	Comments	Model includes treatment+log transformed baseline value+stratification factor (screening eos count [<150, 150-<300, >=300 cells/uL])
Method of Estimation	Estimation Parameter	Ratio of Geometric LSMeans
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 90%; 0.90 to 1.40
	Parameter Dispersion	Type: Value:
	Estimation Comments	Parameter: T cells CD3+ (cells/mm^2)
Other Statistical Analysis		95% CI (0.86, 1.46)

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Teze 210 mg Q4W, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.216
	Comments	Nominal p-values were reported. No adjustment of multiplicity was performed.
	Method	ANCOVA
	Comments	Model includes treatment+log transformed baseline value+stratification factor (screening eos count [<150, 150-<300, >=300 cells/uL])
Method of Estimation	Estimation Parameter	Ratio of Geometric LSMeans
	Estimated Value	1.18
	Confidence Interval	(2-Sided) 90%; 0.94 to 1.48
	Parameter Dispersion	Type: Value:
	Estimation Comments	Parameter: T cells CD4+ (cells/mm^2)
Other Statistical Analysis		95% CI (0.90, 1.55)

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Teze 210 mg Q4W, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.260
	Comments	Nominal p-values were reported. No adjustment of multiplicity was performed.
	Method	ANCOVA
	Comments	Model includes treatment+log transformed baseline value+stratification factor (screening eos count [<150, 150-<300, >=300 cells/uL])
Method of Estimation	Estimation Parameter	Ratio of Geometric LSMeans
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 90%; 0.64 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments	Parameter: Mast cells Tryptase+ (cells/mm^2)
Other Statistical Analysis		95% CI (0.61, 1.15)

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Teze 210 mg Q4W, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.546
	Comments	Nominal p-values were reported. No adjustment of multiplicity was performed.
	Method	ANCOVA
	Comments	Model includes treatment+log transformed baseline value+stratification factor (screening eos count [<150, 150-<300, >=300 cells/uL])
Method of Estimation	Estimation Parameter	Ratio of Geometric LSMeans
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 90%; 0.74 to 1.92
	Parameter Dispersion	Type: Value:
	Estimation Comments	Parameter: Mast cells Chymase+ (cells/mm^2)
Other Statistical Analysis		95% CI (0.67, 2.10)

2. Secondary Outcome

Title	Reticular Basement Membrane (RBM) Thickness Ratio Change From Baseline to EOT.
Description	The change from baseline to EOT expressed as a ratio i.e. (EOT/baseline) in RBM thickness, determined by microscopic evaluation of bronchoscopic biopsies.
Time Frame	First dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).

Outcome Measure Data

Analysis Population Description

All subjects randomised to study treatment who completed at least 20 weeks of study treatment and had a baseline assessment and an EOT assessment not greater than 8 weeks after date of last dose of IP.

Arm/Group Title	Teze 210 mg Q4W	Placebo
Arm/Group Description	Tezepelumab subcutaneous injection	Placebo subcutaneous injection
Measure Participants	42	40
Geometric Least Squares Mean (90% Confidence Interval) [Ratio]	0.87	0.90

3. Secondary Outcome

Title	Percent (%) Airway Epithelial Integrity Ratio Change From Baseline to EOT.
Description	The change from baseline to EOT expressed as a ratio i.e. (EOT/baseline) in % airway epithelial, determined by microscopic evaluation of bronchoscopic biopsies.
Time Frame	First dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).

Outcome Measure Data

Analysis Population Description

Number of Participants Analyzed are all subjects randomized to study treatment who completed at least 20 weeks of study treatment and had an EOT visit not greater than 8 weeks after date of last dose of IP. In order to be included in analysis, the participants also had to have a non-missing baseline as well as a non-missing EOT assessment for the respective variable.

Arm/Group Title	Teze 210 mg Q4W	Placebo
Arm/Group Description	Tezepelumab subcutaneous injection	Placebo subcutaneous injection
Measure Participants	54	56
Intact epithelium	0.87	0.84
Damaged epithelium	1.01	0.95
Denuded epithelium	1.05	1.34

Adverse Events

Time Frame	From first dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).
Arm/Group Title	Placebo		Teze 210 mg Q4W
Arm/Group Description	Placebo subcutaneous injection		Tezepelumab subcutaneous injection
All Cause Mortality
	Placebo		Teze 210 mg Q4W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/57 (0%)		0/59 (0%)
Serious Adverse Events
	Placebo		Teze 210 mg Q4W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/57 (12.3%)		3/59 (5.1%)
Cardiac disorders
Myocarditis	1/57 (1.8%)	1	0/59 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/57 (1.8%)	1	0/59 (0%)	0
Gastrooesophageal reflux disease	0/57 (0%)	0	1/59 (1.7%)	1
Hiatus hernia	0/57 (0%)	0	1/59 (1.7%)	1
Infections and infestations
Influenza	0/57 (0%)	0	1/59 (1.7%)	1
Injury, poisoning and procedural complications
Post procedural complication	2/57 (3.5%)	2	0/59 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Meningioma	0/57 (0%)	0	1/59 (1.7%)	1
Pancreatic carcinoma	1/57 (1.8%)	1	0/59 (0%)	0
Squamous cell carcinoma	1/57 (1.8%)	1	0/59 (0%)	0
Renal and urinary disorders
Urinary retention	1/57 (1.8%)	1	0/59 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	1/57 (1.8%)	1	0/59 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Teze 210 mg Q4W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	45/57 (78.9%)		48/59 (81.4%)
Eye disorders
Dry eye	0/57 (0%)	0	2/59 (3.4%)	2
Gastrointestinal disorders
Diarrhoea	0/57 (0%)	0	5/59 (8.5%)	6
Nausea	2/57 (3.5%)	2	2/59 (3.4%)	2
Vomiting	3/57 (5.3%)	3	2/59 (3.4%)	2
General disorders
Influenza like illness	3/57 (5.3%)	3	3/59 (5.1%)	3
Injection site erythema	2/57 (3.5%)	12	5/59 (8.5%)	14
Injection site granuloma	0/57 (0%)	0	2/59 (3.4%)	2
Injection site pruritus	1/57 (1.8%)	1	4/59 (6.8%)	5
Oedema peripheral	0/57 (0%)	0	3/59 (5.1%)	3
Pyrexia	0/57 (0%)	0	3/59 (5.1%)	3
Infections and infestations
Bronchitis	0/57 (0%)	0	2/59 (3.4%)	2
Candida infection	0/57 (0%)	0	2/59 (3.4%)	2
Chronic sinusitis	2/57 (3.5%)	2	0/59 (0%)	0
Conjunctivitis	0/57 (0%)	0	2/59 (3.4%)	2
Gastroenteritis	2/57 (3.5%)	2	1/59 (1.7%)	1
Lower respiratory tract infection	1/57 (1.8%)	1	2/59 (3.4%)	2
Lower respiratory tract infection bacterial	2/57 (3.5%)	2	1/59 (1.7%)	1
Nasopharyngitis	21/57 (36.8%)	22	22/59 (37.3%)	28
Oral candidiasis	0/57 (0%)	0	2/59 (3.4%)	4
Pneumonia	1/57 (1.8%)	1	2/59 (3.4%)	2
Rhinitis	2/57 (3.5%)	2	1/59 (1.7%)	1
Sinusitis	2/57 (3.5%)	2	0/59 (0%)	0
Tonsillitis	0/57 (0%)	0	2/59 (3.4%)	2
Upper respiratory tract infection	4/57 (7%)	4	3/59 (5.1%)	3
Urinary tract infection	2/57 (3.5%)	5	3/59 (5.1%)	4
Injury, poisoning and procedural complications
Contusion	0/57 (0%)	0	2/59 (3.4%)	5
Fall	1/57 (1.8%)	1	2/59 (3.4%)	4
Post procedural complication	10/57 (17.5%)	12	11/59 (18.6%)	11
Post procedural fever	2/57 (3.5%)	2	4/59 (6.8%)	4
Procedural pain	0/57 (0%)	0	3/59 (5.1%)	3
Musculoskeletal and connective tissue disorders
Arthralgia	3/57 (5.3%)	4	3/59 (5.1%)	3
Back pain	2/57 (3.5%)	2	2/59 (3.4%)	2
Bursitis	2/57 (3.5%)	2	0/59 (0%)	0
Musculoskeletal chest pain	2/57 (3.5%)	3	1/59 (1.7%)	1
Myalgia	1/57 (1.8%)	1	3/59 (5.1%)	3
Nervous system disorders
Headache	8/57 (14%)	8	6/59 (10.2%)	9
Respiratory, thoracic and mediastinal disorders
Cough	4/57 (7%)	5	6/59 (10.2%)	9
Dysphonia	2/57 (3.5%)	2	2/59 (3.4%)	2
Nasal congestion	2/57 (3.5%)	2	1/59 (1.7%)	1
Oropharyngeal pain	2/57 (3.5%)	2	6/59 (10.2%)	6
Vascular disorders
Hypertension	2/57 (3.5%)	2	1/59 (1.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS 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.