FLAVOUR: AZD5718 Phase IIa Study to Evaluate Efficacy, Safety and Tolerability of Oral AZD5718 in Patients With Coronary Artery Disease (CAD).

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03317002
• Collaborator: (none)
• Enrollment: 129
• Locations: 9
• Arms: 3
• Actual Duration (Months): 29.3
• Patients Per Site: 14.3
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This is a randomized, single-blind, placebo-controlled, parallel-group, multicentre study in patients with CAD. The study will be conducted at approximately 10 centres in 3 countries. Approximately 138 CAD patients will be randomized to AZD5718 or placebo (treatment duration 12 weeks).

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease	Drug: AZD5718; Drug: AZD5718; Drug: Placebo	Phase 2

Detailed Description

This is a randomized, single-blind, placebo-controlled, parallel-group, multicentre study in patients with CAD. The study will be conducted at approximately 10 centres in 3 countries (Denmark, Finland and Sweden).

Patients suitable for the study will be identified and screened for eligibility after being hospitalized for Acute Coronary Syndrome (ACS) (Visit 1) comprising ST Elevation Myocardial Infarction (STEMI) or Non-ST Elevation Myocardial Infarction (non-STEMI). At Visit 1, after signing informed consent, study measurements will take place at days 1, 2, 3 and 5 post ACS, where feasible. It is planned that approximately 138 CAD patients will be randomized to ensure at least 66 evaluable patients receiving AZD5718 Dose B or placebo are included with 12 weeks treatment. For supporting dose selection in future studies, a treatment arm with 28 randomized patients receiving AZD5718 Dose A is included in the study. The study was originally designed to be a 4-week study and was amended to be a 12-week study. Therefore, the total number of patients is greater than required for a 12 weeks study (about 100), since some patients will only have 4 weeks of treatment.

An evaluable patient is defined as a patient with a valid Coronary Flow Velocity Reserve (CFVR) measurement at Visit 2 and one post baseline visit as judged by the CFVR Core lab.

On Day 1 (Visit 2), 7 to 28 days after the ACS event, patients willing to participate in the study will complete the screening procedure and, if eligible, be randomized. Treatment duration will be 12 weeks. During the treatment phase, patients will come in to the clinic for study measurements at 2 weeks (visit 3), 4 weeks (visit 4), 8 weeks (visit 4b) and 12 weeks (visit 4c).

A follow-up visit (Visit 5) will be performed at 4 weeks (±4 days) after last dose in order to ensure safety and well-being of the patients

Study Design

• Study Type: Interventional
• Actual Enrollment: 129 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A 12-week, Randomized, Single-blind, Placebo-controlled, Multi-centre, Parallel Group, Phase IIa Study to Evaluate Efficacy, Safety and Tolerability of Oral AZD5718 After 4 and 12-weeks of Treatment in Patients With Coronary Artery Disease (CAD)
• Actual Study Start Date: Oct 30, 2017
• Actual Primary Completion Date: Apr 8, 2020
• Actual Study Completion Date: Apr 8, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AZD5718 Dose A AZD5718 Dose A once daily	Drug: AZD5718; Oral dose of AZD5718 (tablet)
Experimental: AZD5718 Dose B AZD5718 Dose B once daily	Drug: AZD5718; Oral dose of AZD5718 (tablet)
Placebo Comparator: Placebo Matching placebo once daily	Drug: Placebo; Matching placebo (tablet)

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Creatinine-normalized u-LTE4 at Week 4 [Baseline and 4 weeks]

   Creatinine-normalized u-LTE4 is calculated as uLTE4/creatinine

Secondary Outcome Measures

1. Change From Baseline in Creatinine-normalized u-LTE4 at Week 12 [Baseline and 12 weeks]

   Creatinine-normalized u-LTE4 is calculated as uLTE4/creatinine

2. Change From Baseline in CFVR at Week 12 [Baseline and 12 weeks]

   CFVR = Coronary Flow Velocity Reserve = LAD(hyperaemic)/LAD(rest)

3. Change From Baseline in CFVR at Week 4 [Baseline and 4 weeks]

   CFVR = Coronary Flow Velocity Reserve = LAD(hyperaemic)/LAD(rest)

4. Summary of Plasma Concentrations of AZD5718 [16 weeks]

5. Change From Baseline in LAD Hypereamic Flow at 4 Weeks [Baseline and 4 weeks]

   LAD=Left Anterior Descending

6. Change From Baseline in LVEF at 4 Weeks [Baseline and 4 weeks]

   LVEF=Left Ventricular Ejection Fraction

7. Change From Baseline in LV Longitudinal Early Diastolic Strain Rate at 4 Weeks [Baseline and 4 weeks]

   LV=Left Ventricular

8. Change From Baseline in LV-GLS at Rest at Week 4 [Baseline and 4 weeks]

   LV-GLS = Left Ventricular Global Longitudinal Strain

9. Change From Baseline in LV-GCS at Rest at Week 4 [Baseline and 4 weeks]

   LV-GCS = Left Ventricular Global Circumferential Strain

10. Change From Baseline in LAD Resting Mean Diastolic Flow Velocity at 4 Weeks [Baseline and 4 weeks]

    LAD=Left Anterior Descending

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Males and females of non-childbearing potential

• Age ≥18 to ≤75

• Body Mass Index (BMI) ≥18 to ≤35 kg/m2

• CAD patients, here defined as:

ACS 7-28 days prior to study randomization (ACS defined as STEMI, non STEMI event documented by Electrocardiogram (ECG), cardiac enzymes [troponin] and angiogram) Provision of signed and dated, written informed consent prior to any study specific procedures

Exclusion Criteria:

• Uncontrolled Type 1 or Type 2 diabetes defined as haemoglobin A1c (HbA1c) Diabetes

• Control and Complications Trial (DCCT)> 9% or International Federation of Clinical Chemistry (IFCC) >74.9 mmol/mol

• Patients with atrial fibrillation (chronic or current) or history of ventricular tachycardia requiring therapy for termination, or symptomatic sustained ventricular tachycardia or sick sinus syndrome or Atrioventricular blockage degree 2-3

• Prior coronary artery by-pass graft (Coronary artery bypass grafting) to Left Anterior Descending artery (LAD)

• Left ventricle ejection fraction < 30%

• Unacceptable level of angina despite maximal medical therapy or unstable angina at entry

• Canadian Cardiovascular Society (CCS) ≥ 3 (Visit 1 or Visit 2)

• Stroke within the previous 6 months from ACS or ongoing treatment with Persantin or Asasantin

• Chronic use of anticoagulants on therapeutic dose (not including thrombosis prophylaxis) during the study

• Planned additional cardiac intervention (e.g., Percutaneous coronary intervention (PCI), Coronary artery bypass grafting (CABG) within next 6 months

• New York Heart Association (NYHA) class III-IV heart failure or decompensated heart failure at discharge or hospitalization for exacerbation of chronic heart failure within the previous 3 months from ACS

• Previously known severe renal disease (Chronic Kidney Disease (CKD) stage 4 or 5) or previously known creatinine clearance calculated by Cockcroft Gault equation <30 ml/min*m2

• Known allergy to adenosine and mannitol, or experience of previous adverse effects of adenosine stress testing.

• Participation in another interventional clinical study with an investigational pharmaceutical product during the last 3 months also including drug eluting stents.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Aarhus		Denmark	8200
2	Research Site	Frederiksberg		Denmark	2000
3	Research Site	Odense C		Denmark	5000
4	Research Site	Kuopio		Finland	70210
5	Research Site	Turku		Finland	20520
6	Research Site	Göteborg		Sweden	413 45
7	Research Site	Lund		Sweden	222 42
8	Research Site	Stockholm		Sweden	171 76
9	Research Site	Uppsala		Sweden	75185

Sponsors and Collaborators

• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Feb 11, 2019
• Statistical Analysis Plan - May 18, 2020

More Information

Additional Information:

• redacted Statistical Analysis Plan
• redacted Clinical Study Protocol

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT03317002
• Other Study ID Numbers: D7550C00003
• First Posted: Oct 23, 2017
• Last Update Posted: Jun 30, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease

Study Results

Participant Flow

Recruitment Details	The study was conducted in 3 countries at 9 sites; 3 in Denmark, 2 in Finland and 4 in Sweden.
Pre-assignment Detail	Participants underwent a screening visit between 2 and within 27 days before receiving the first dose of IP.

Arm/Group Title	AZD5718 (200 mg)	AZD5718 (50 mg)	Placebo
Arm/Group Description	AZD5718 (200 mg)	AZD5718 (50 mg)	Placebo
Period Title: Overall Study
STARTED	52	25	52
COMPLETED	50	24	51
NOT COMPLETED	2	1	1

Baseline Characteristics

Arm/Group Title	AZD5718 (200 mg)	AZD5718 (50 mg)	Placebo	Total
Arm/Group Description	AZD5718 (200 mg)	AZD5718 (50 mg)	Placebo	Total of all reporting groups
Overall Participants	52	25	51	128
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	61.9 (8.21)	61.4 (8.12)	61.1 (8.51)	61.5 (8.26)
Sex: Female, Male (Count of Participants)
Female	7 13.5%	0 0%	10 19.6%	17 13.3%
Male	45 86.5%	25 100%	41 80.4%	111 86.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 1.9%	0 0%	0 0%	1 0.8%
Not Hispanic or Latino	51 98.1%	25 100%	51 100%	127 99.2%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	1 2%	1 0.8%
White	52 100%	25 100%	50 98%	127 99.2%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Creatinine-normalized u-LTE4 at Week 4
Description	Creatinine-normalized u-LTE4 is calculated as uLTE4/creatinine
Time Frame	Baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

Number of participants analysed differs from participant flow module due to missing data

Arm/Group Title	AZD5718 (200 mg)	AZD5718 (50 mg)	Placebo
Arm/Group Description	AZD5718 (200 mg)	AZD5718 (50 mg)	Placebo
Measure Participants	49	24	50
Geometric Mean (Geometric Coefficient of Variation) [Ratio]	0.04 (92.55)	0.09 (84.32)	1.09 (44.38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AZD5718 (200 mg), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.04
	Confidence Interval	(1-Sided) 95%; to 0.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	AZD5718 (50 mg), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.08
	Confidence Interval	(1-Sided) 95%; to 0.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Creatinine-normalized u-LTE4 at Week 12
Description	Creatinine-normalized u-LTE4 is calculated as uLTE4/creatinine
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Number of participants analysed differs from participant flow module due to missing data

Arm/Group Title	AZD5718 (200 mg)	AZD5718 (50 mg)	Placebo
Arm/Group Description	AZD5718 (200 mg)	AZD5718 (50 mg)	Placebo
Measure Participants	29	18	36
Geometric Mean (Geometric Coefficient of Variation) [Ratio]	0.04 (92.55)	0.09 (84.32)	1.09 (44.38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AZD5718 (200 mg), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.04
	Confidence Interval	(1-Sided) 95%; to 0.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	AZD5718 (50 mg), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.09
	Confidence Interval	(1-Sided) 95%; to 0.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in CFVR at Week 12
Description	CFVR = Coronary Flow Velocity Reserve = LAD(hyperaemic)/LAD(rest)
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Number of participants analysed differs from participant flow module due to missing data

Arm/Group Title	AZD5718 (200 mg)	AZD5718 (50 mg)	Placebo
Arm/Group Description	AZD5718 (200 mg)	AZD5718 (50 mg)	Placebo
Measure Participants	16	11	24
Geometric Mean (Geometric Coefficient of Variation) [Ratio]	0.93 (23.64)	0.98 (39.53)	1.16 (33.46)

4. Secondary Outcome

Title	Change From Baseline in CFVR at Week 4
Description	CFVR = Coronary Flow Velocity Reserve = LAD(hyperaemic)/LAD(rest)
Time Frame	Baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

Number of participants analysed differs from participant flow module due to missing data

Arm/Group Title	AZD5718 (200 mg)	AZD5718 (50 mg)	Placebo
Arm/Group Description	AZD5718 (200 mg)	AZD5718 (50 mg)	Placebo
Measure Participants	36	16	38
Geometric Mean (Geometric Coefficient of Variation) [Ratio]	1.03 (28.34)	1.15 (31.47)	1.08 (33.16)

5. Secondary Outcome

Title	Summary of Plasma Concentrations of AZD5718
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

Number of participants analysed differs from participant flow module due to missing data

Arm/Group Title	AZD5718 (200 mg)	AZD5718 (50 mg)
Arm/Group Description	AZD5718 (200 mg)	AZD5718 (50 mg)
Measure Participants	52	25
Baseline: 1-8 Hours Post-Dose	611.88 (234.50)	47.88 (497.86)
2 weeks (Visit 3): 20-28 Hours Post-Dose	59.36 (90.97)	16.57 (127.80)
4 weeks (Visit 4): Pre-Dose	48.00 (68.17)	11.01 (60.70)
4 weeks (Visit 4): 0-2 Hours Post-Dose	339.28 (243.04)	38.68 (159.56)
4 weeks (Visit 4): 2-4 Hours Post-Dose	919.22 (51.26)	148.64 (71.86)
4 weeks (Visit 4): 4-8 Hours Post-Dose	649.09 (49.89)	105.40 (52.16)
12 weeks (Visit 4c): Pre-Dose	65.39 (91.52)	13.97 (88.12)
16 weeks (Visit 5) - FUP 1 month	0.51 (16.39)	0.50 (0.00)

6. Secondary Outcome

Title	Change From Baseline in LAD Hypereamic Flow at 4 Weeks
Description	LAD=Left Anterior Descending
Time Frame	Baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

Number of participants analysed differs from participant flow module due to missing data

Arm/Group Title	AZD5718 (200 mg)	AZD5718 (50 mg)	Placebo
Arm/Group Description	AZD5718 (200 mg)	AZD5718 (50 mg)	Placebo
Measure Participants	36	16	38
Mean (Standard Deviation) [m/sec]	0.02 (0.16)	0.04 (0.16)	0.03 (0.17)

7. Secondary Outcome

Title	Change From Baseline in LVEF at 4 Weeks
Description	LVEF=Left Ventricular Ejection Fraction
Time Frame	Baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

Number of participants analysed differs from participant flow module due to missing data

Arm/Group Title	AZD5718 (200 mg)	AZD5718 (50 mg)	Placebo
Arm/Group Description	AZD5718 (200 mg)	AZD5718 (50 mg)	Placebo
Measure Participants	46	22	45
Mean (Standard Deviation) [percent LVEF]	-0.23 (5.30)	2.70 (6.39)	0.48 (5.00)

8. Secondary Outcome

Title	Change From Baseline in LV Longitudinal Early Diastolic Strain Rate at 4 Weeks
Description	LV=Left Ventricular
Time Frame	Baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

Number of participants analysed differs from participant flow module due to missing data

Arm/Group Title	AZD5718 (200 mg)	AZD5718 (50 mg)	Placebo
Arm/Group Description	AZD5718 (200 mg)	AZD5718 (50 mg)	Placebo
Measure Participants	43	19	44
Geometric Mean (Geometric Coefficient of Variation) [1/s]	1.02 (30.61)	0.98 (33.55)	1.03 (30.45)

9. Secondary Outcome

Title	Change From Baseline in LV-GLS at Rest at Week 4
Description	LV-GLS = Left Ventricular Global Longitudinal Strain
Time Frame	Baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

Number of participants analysed differs from participant flow module due to missing data

Arm/Group Title	AZD5718 (200 mg)	AZD5718 (50 mg)	Placebo
Arm/Group Description	AZD5718 (200 mg)	AZD5718 (50 mg)	Placebo
Measure Participants	43	17	42
Mean (Standard Deviation) [Percent LV-GLS]	-0.41 (3.00)	0.34 (2.47)	-0.63 (2.61)

10. Secondary Outcome

Title	Change From Baseline in LV-GCS at Rest at Week 4
Description	LV-GCS = Left Ventricular Global Circumferential Strain
Time Frame	Baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

Number of participants analysed differs from participant flow module due to missing data

Arm/Group Title	AZD5718 (200 mg)	AZD5718 (50 mg)	Placebo
Arm/Group Description	AZD5718 (200 mg)	AZD5718 (50 mg)	Placebo
Measure Participants	39	16	34
Mean (Standard Deviation) [Percent]	0.34 (7.24)	1.71 (5.40)	-1.88 (6.78)

11. Secondary Outcome

Title	Change From Baseline in LAD Resting Mean Diastolic Flow Velocity at 4 Weeks
Description	LAD=Left Anterior Descending
Time Frame	Baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

Number of participants analysed differs from participant flow module due to missing data

Arm/Group Title	AZD5718 (200 mg)	AZD5718 (50 mg)	Placebo
Arm/Group Description	AZD5718 (200 mg)	AZD5718 (50 mg)	Placebo
Measure Participants	36	16	38
Geometric Mean (Geometric Coefficient of Variation) [m/sec]	1.01 (23.31)	0.92 (23.68)	0.99 (20.14)

Adverse Events

Time Frame	Treatment period, up to 12 weeks
Arm/Group Title	AZD5718 (200 mg)		AZD5718 (50 mg)		Placebo
Arm/Group Description	AZD5718 (200 mg)		AZD5718 (50 mg)		Placebo
All Cause Mortality
	AZD5718 (200 mg)		AZD5718 (50 mg)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/52 (0%)		0/25 (0%)		0/51 (0%)
Serious Adverse Events
	AZD5718 (200 mg)		AZD5718 (50 mg)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/52 (7.7%)		3/25 (12%)		4/51 (7.8%)
Cardiac disorders
Acute myocardial infarction	0/52 (0%)		1/25 (4%)		0/51 (0%)
Angina pectoris	0/52 (0%)		1/25 (4%)		0/51 (0%)
Ventricular fibrillation	0/52 (0%)		1/25 (4%)		0/51 (0%)
Gastrointestinal disorders
Pancreatitis acute	0/52 (0%)		1/25 (4%)		0/51 (0%)
General disorders
Chest pain	2/52 (3.8%)		0/25 (0%)		1/51 (2%)
Non-cardiac chest pain	0/52 (0%)		1/25 (4%)		0/51 (0%)
Infections and infestations
Post procedural sepsis	1/52 (1.9%)		0/25 (0%)		0/51 (0%)
Musculoskeletal and connective tissue disorders
Pain in extremity	0/52 (0%)		0/25 (0%)		1/51 (2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer	1/52 (1.9%)		0/25 (0%)		0/51 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/52 (0%)		0/25 (0%)		1/51 (2%)
Pulmonary oedema	0/52 (0%)		0/25 (0%)		1/51 (2%)
Other (Not Including Serious) Adverse Events
	AZD5718 (200 mg)		AZD5718 (50 mg)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/52 (51.9%)		12/25 (48%)		22/51 (43.1%)
Blood and lymphatic system disorders
Anaemia	4/52 (7.7%)		0/25 (0%)		2/51 (3.9%)
Gastrointestinal disorders
Nausea	1/52 (1.9%)		1/25 (4%)		2/51 (3.9%)
Diarrhoea	2/52 (3.8%)		1/25 (4%)		4/51 (7.8%)
General disorders
Chest pain	3/52 (5.8%)		1/25 (4%)		3/51 (5.9%)
Fatigue	3/52 (5.8%)		1/25 (4%)		0/51 (0%)
Infections and infestations
Nasopharyngitis	6/52 (11.5%)		4/25 (16%)		7/51 (13.7%)
Injury, poisoning and procedural complications
Contusion	2/52 (3.8%)		1/25 (4%)		1/51 (2%)
Investigations
Alanine aminotransferase increased	0/52 (0%)		0/25 (0%)		4/51 (7.8%)
Musculoskeletal and connective tissue disorders
Myalgia	3/52 (5.8%)		0/25 (0%)		1/51 (2%)
Nervous system disorders
Dizziness	5/52 (9.6%)		2/25 (8%)		4/51 (7.8%)
Headache	1/52 (1.9%)		1/25 (4%)		2/51 (3.9%)
Psychiatric disorders
Anxiety	2/52 (3.8%)		1/25 (4%)		1/51 (2%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	6/52 (11.5%)		4/25 (16%)		7/51 (13.7%)
Cough	5/52 (9.6%)		0/25 (0%)		1/51 (2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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