Efficacy and Safety of LCZ696 200 mg + Amlodipine 5 mg in Comparison With Amlodipine 5 mg in Hypertensive Patients Not Responding to Amlodipine

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01663233
• Collaborator: (none)
• Enrollment: 266
• Locations: 28
• Arms: 2
• Duration (Months): 9
• Patients Per Site: 9.5
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

This study will assess whether LCZ696 when used in combination with amlodipine will provide greater BP lowering benefit compared to amlodipine alone in Asian hypertensive patients not adequately responsive to amlodipine therapy.

Condition or Disease	Intervention/Treatment	Phase
Essential Hypertension	Drug: LCZ696; Drug: Amlodipine; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 266 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, 8-week, Double-blind, Parallel-group, Active-controlled, Multicenter Study to Evaluate the Efficacy and Safety of the Combination of LCZ696 200 mg + Amlodipine 5 mg in Comparison With Amlodipine 5 mg in Patients With Essential Hypertension Not Adequately Responsive to Amlodipine 5 mg Monotherapy Treatment
• Study Start Date: Aug 1, 2012
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LCZ696 and amlodipine Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (had an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.	Drug: LCZ696; LCZ696 will use tablets available at a strength of 200mg. Patients will be instructed to take the prescribed medication once a day.; Drug: Amlodipine; Amlodipine will use tablets available at a strength of 5 mg. Patients will be instructed to take the prescribed medication once a day.
Active Comparator: Amlodipine Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (had an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.	Drug: Amlodipine; Amlodipine will use tablets available at a strength of 5 mg. Patients will be instructed to take the prescribed medication once a day.; Drug: Placebo; Matching placebo to LCZ696

Outcome Measures

Primary Outcome Measures

1. Change in Mean 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Systolic Blood Pressure (maSBP) [8 weeks]

   The change in mean 24 hour ambulatory systolic blood pressure (maSBP) from baseline to end of the study (week 8) in the 2 groups was measured. A greater reduction from baseline in the LCZ696 group indicates a positive treatment effect.

Secondary Outcome Measures

1. Change in Mean 24-hour ABPM Diastolic Blood Pressure (maDBP) [8 weeks]

   The change in mean 24 hour maDBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect.

2. Change in Mean Sitting Systolic Blood Pressure (msSBP) [8 weeks]

   The change in the patient's msSBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect.

3. Change in Mean Sitting Diastolic Blood Pressure (msDBP) [8 weeks]

   The change in the patient's msDBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect.

4. Change in Sitting Pulse Pressure (PP) [8 weeks]

   The change in the patient's mean sitting PP from baseline to end of the study was measured. Pulse pressure measures the difference in mean sitting systolic blood pressure and mean sitting diastolic blood pressure.

5. Number of Participants Achieving Systolic and Diastolic Blood Pressure Control (< 140/90 mmHg) [8 weeks]

   The number of participants achieving a systolic and diastolic blood pressure < 140/90 mmHg was measured. This outcome measure shows how well a given blood pressure treatment can achieve a given blood pressure target or goal. Participants who achieved the target blood pressure were determined based on the mean SBP and DBP measurements taken at the end of the study. If the participants' BP measurement was below the above target, they were considered to have successful blood pressure control.

6. Number of Participants Achieving Successful Response in msSBP (< 140 mmHg or a Reduction ≥ 20 mmHg From Baseline) [8 weeks]

   The number of participants who achieved successful treatment response in the msSBP of < 140mmHg or a reduction ≥ 20 mmHg from baseline after completing study treatment was measured. Participants who achieved either of the above targets were deemed as a having a successful response.

7. Number of Participants Achieving Successful Response in msDBP (< 90 mmHg or a Reduction ≥ 10 mmHg From Baseline) [8 weeks of treatment]

   The number of participants who achieved successful treatment response in msDBP of < 90mmHg or a reduction ≥ 10mmHg from baseline after completing study treatment was measured. Participants who achieved either of the above targets were deemed as having a successful response.

8. Number of Participants With Adverse Event [8 weeks]

   Participants were monitored for adverse events, serious adverse events and death.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

Patients must give written informed consent and have a diagnosis of hypertension:

Untreated patients must have an msSBP ≥ 150 mmHg and < 180 mmHg at both Visit 1 and Visit 101. Pre-treated patients must have an msSBP ≥ 145 mmHg and < 180 mmHg after wash out at Visit 101. All patients must have an office msSBP ≥ 145 mmHg and < 180 mmHg at the completion of the 4-week run-in epoch (at the randomization visit (Visit 201).

Patients must successfully complete ABPM and pass technical requirements at Visit 201.

Exclusion Criteria:

Malignant or severe hypertension (grade 3 of WHO classification; msDBP ≥110 mmHg and/or msSBP ≥ 180 mmHg).

History of angioedema, drug-related or otherwise. History or evidence of a secondary form of hypertension. Transient ischemic cerebral attack (TIA) during the 12 months prior to Visit 1 or any history of stroke.

History of myocardial infarction, coronary bypass surgery or PCI during the 12 months prior to Visit 1

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Shijiazhuang	Hebei	China	050000
2	Novartis Investigative Site	Chongqing		China	400042
3	Novartis Investigative Site	Shanghai		China	200025
4	Novartis Investigative Site	Tianjin		China	300142
5	Novartis Investigative Site	Edogawa-ku	Tokyo	Japan	133-0061
6	Novartis Investigative Site	Katsushika-ku	Tokyo	Japan	124-0024
7	Novartis Investigative Site	Kiyose-city	Tokyo	Japan	204-0021
8	Novartis Investigative Site	Kunitachi	Tokyo	Japan	186-0001
9	Novartis Investigative Site	Shibuya-ku	Tokyo	Japan	150-0002
10	Novartis Investigative Site	Shinagawa-ku	Tokyo	Japan	142-0063
11	Novartis Investigative Site	Toshima-ku	Tokyo	Japan	171-0021
12	Novartis Investigative Site	Wonju	Gangwon-Do	Korea, Republic of	220-701
13	Novartis Investigative Site	Koyang	Kyunggi	Korea, Republic of	410-719
14	Novartis Investigative Site	Busan		Korea, Republic of	602-739
15	Novartis Investigative Site	Daegu		Korea, Republic of	705-703
16	Novartis Investigative Site	Daegu		Korea, Republic of	705-718
17	Novartis Investigative Site	Seoul		Korea, Republic of	150-713
18	Novartis Investigative Site	Kuching	Sarawak	Malaysia	94300
19	Novartis Investigative Site	Kuala Lumpur		Malaysia	56000
20	Novartis Investigative Site	Quezon City	Manila	Philippines	1100
21	Novartis Investigative Site	Manila	Metro Manila	Philippines	1000
22	Novartis Investigative Site	Quezon City		Philippines	1100
23	Novartis Investigative Site	Quezon City		Philippines	1102
24	Novartis Investigative Site	Valenzuela City		Philippines	1441
25	Novartis Investigative Site	Taipei	Taiwan, ROC	Taiwan	112
26	Novartis Investigative Site	Taichung		Taiwan	40447
27	Novartis Investigative Site	Taipei		Taiwan	10002
28	Novartis Investigative Site	Taipei		Taiwan	114

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01663233
• Other Study ID Numbers: CLCZ696A2319
• First Posted: Aug 13, 2012
• Last Update Posted: Oct 23, 2015
• Last Verified: Oct 1, 2015

• Keywords provided by Novartis Pharmaceuticals: Essential hypertension; High blood pressure
• Additional relevant MeSH terms: Hypertension; Essential Hypertension; Amlodipine; Sacubitril and valsartan sodium hydrate drug combination

Study Results

Participant Flow

Arm/Group Title	LCZ696 and Amlodipine	Amlodipine
Arm/Group Description	Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.	Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.
Period Title: Overall Study
STARTED	130	136
COMPLETED	126	129
NOT COMPLETED	4	7

Baseline Characteristics

Arm/Group Title	LCZ696 and Amlodipine	Amlodipine	Total
Arm/Group Description	Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.	Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.	Total of all reporting groups
Overall Participants	130	136	266
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	55.4 (9.31)	55.5 (9.43)	55.4 (9.35)
Sex: Female, Male (Count of Participants)
Female	49 37.7%	61 44.9%	110 41.4%
Male	81 62.3%	75 55.1%	156 58.6%

Outcome Measures

1. Primary Outcome

Title	Change in Mean 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Systolic Blood Pressure (maSBP)
Description	The change in mean 24 hour ambulatory systolic blood pressure (maSBP) from baseline to end of the study (week 8) in the 2 groups was measured. A greater reduction from baseline in the LCZ696 group indicates a positive treatment effect.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

FAS: This set included all randomized participants who received at least one dose of study medication. Among the 266 Full Analysis Set (FAS) participants, 251 participants (123 participants in the LCZ696 + amlodipine group and 128 participants in the amlodipine group) had eligible ABPM at both baseline and endpoint.

Arm/Group Title	LCZ696 and Amlodipine	Amlodipine
Arm/Group Description	Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.	Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.
Measure Participants	123	128
Least Squares Mean (Standard Error) [mmHg]	-13.93 (0.56)	-0.82 (0.56)

2. Secondary Outcome

Title	Change in Mean 24-hour ABPM Diastolic Blood Pressure (maDBP)
Description	The change in mean 24 hour maDBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

FAS: This set included all randomized participants who received at least one dose of study medication. Among the 266 Full Analysis Set (FAS) participants, 251 participants (123 participants in the LCZ696 + amlodipine group and 128 participants in the amlodipine group) had eligible ABPM at both baseline and endpoint.

Arm/Group Title	LCZ696 and Amlodipine	Amlodipine
Arm/Group Description	Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.	Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.
Measure Participants	123	128
Least Squares Mean (Standard Error) [mmHg]	-8.03 (0.38)	-0.33 (0.37)

3. Secondary Outcome

Title	Change in Mean Sitting Systolic Blood Pressure (msSBP)
Description	The change in the patient's msSBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	LCZ696 and Amlodipine	Amlodipine
Arm/Group Description	Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.	Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.
Measure Participants	130	136
Least Squares Mean (Standard Error) [mmHg]	-19.60 (1.35)	-9.34 (1.33)

4. Secondary Outcome

Title	Change in Mean Sitting Diastolic Blood Pressure (msDBP)
Description	The change in the patient's msDBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	LCZ696 and Amlodipine	Amlodipine
Arm/Group Description	Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.	Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.
Measure Participants	130	136
Least Squares Mean (Standard Error) [mmHg]	-9.22 (0.83)	-3.96 (0.82)

5. Secondary Outcome

Title	Change in Sitting Pulse Pressure (PP)
Description	The change in the patient's mean sitting PP from baseline to end of the study was measured. Pulse pressure measures the difference in mean sitting systolic blood pressure and mean sitting diastolic blood pressure.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	LCZ696 and Amlodipine	Amlodipine
Arm/Group Description	Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.	Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.
Measure Participants	130	136
Least Squares Mean (Standard Error) [mmHg]	-10.31 (0.90)	-5.46 (0.89)

6. Secondary Outcome

Title	Number of Participants Achieving Systolic and Diastolic Blood Pressure Control (< 140/90 mmHg)
Description	The number of participants achieving a systolic and diastolic blood pressure < 140/90 mmHg was measured. This outcome measure shows how well a given blood pressure treatment can achieve a given blood pressure target or goal. Participants who achieved the target blood pressure were determined based on the mean SBP and DBP measurements taken at the end of the study. If the participants' BP measurement was below the above target, they were considered to have successful blood pressure control.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	LCZ696 and Amlodipine	Amlodipine
Arm/Group Description	Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.	Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.
Measure Participants	130	136
Number [Participants]	89 68.5%	46 33.8%

7. Secondary Outcome

Title	Number of Participants Achieving Successful Response in msSBP (< 140 mmHg or a Reduction ≥ 20 mmHg From Baseline)
Description	The number of participants who achieved successful treatment response in the msSBP of < 140mmHg or a reduction ≥ 20 mmHg from baseline after completing study treatment was measured. Participants who achieved either of the above targets were deemed as a having a successful response.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	LCZ696 and Amlodipine	Amlodipine
Arm/Group Description	Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.	Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.
Measure Participants	130	136
Number [Participants]	98 75.4%	53 39%

8. Secondary Outcome

Title	Number of Participants Achieving Successful Response in msDBP (< 90 mmHg or a Reduction ≥ 10 mmHg From Baseline)
Description	The number of participants who achieved successful treatment response in msDBP of < 90mmHg or a reduction ≥ 10mmHg from baseline after completing study treatment was measured. Participants who achieved either of the above targets were deemed as having a successful response.
Time Frame	8 weeks of treatment

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	LCZ696 and Amlodipine	Amlodipine
Arm/Group Description	Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.	Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.
Measure Participants	130	136
Number [Participants]	112 86.2%	95 69.9%

9. Secondary Outcome

Title	Number of Participants With Adverse Event
Description	Participants were monitored for adverse events, serious adverse events and death.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Safety Set: The safety set included all randomized participants who received at least one dose of study medication.

Arm/Group Title	LCZ696 and Amlodipine	Amlodipine
Arm/Group Description	Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.	Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.
Measure Participants	130	136
Adverse Events (serious and non-serious)	26 20%	29 21.3%
Serious Adverse Events	0 0%	0 0%
Deaths	0 0%	0 0%

Adverse Events

Arm/Group Title	LCZ696 and Amlodipine		Amlodipine
Arm/Group Description	Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.		Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.
All Cause Mortality
	LCZ696 and Amlodipine		Amlodipine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	LCZ696 and Amlodipine		Amlodipine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/130 (0%)		0/136 (0%)
Other (Not Including Serious) Adverse Events
	LCZ696 and Amlodipine		Amlodipine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/130 (10%)		19/136 (14%)
Infections and infestations
NASOPHARYNGITIS	5/130 (3.8%)		5/136 (3.7%)
UPPER RESPIRATORY TRACT INFECTION	3/130 (2.3%)		5/136 (3.7%)
Metabolism and nutrition disorders
DYSLIPIDAEMIA	0/130 (0%)		5/136 (3.7%)
HYPOKALAEMIA	2/130 (1.5%)		4/136 (2.9%)
Nervous system disorders
DIZZINESS	3/130 (2.3%)		2/136 (1.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.