Efficacy/Safety of Valsartan Plus Amlodipine and Amlodipine Alone in Patients With Hypertension

• ClinicalTrials.gov Identifier: NCT00413049
• Recruitment Status: Completed
• First Posted: December 19, 2006
• Results First Posted: February 8, 2011
• Last Update Posted: April 29, 2011
• Sponsor: Novartis
• Information provided by: Novartis

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Hypertension
• Interventions: Drug: Valsartan/amlodipine 80/5 mg; Drug: Amlodipine 5 mg
• Enrollment: 698

Participant Flow

Recruitment Details
Pre-assignment Details	Two patients in the valsartan/amlodipine group were excluded from the intent-to-treat population used for the efficacy analyses for having no post-baseline efficacy assessment.

Arm/Group Title	Valsartan/Amlodipine 80/5 mg	Amlodipine 5 mg
Arm/Group Description	1 valsartan/amlodipine 80/5 mg tablet and 1 placebo capsule matching amlodipine 5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.	1 amlodipine 5 mg capsule and 1 placebo tablet matching valsartan/amlodipine 80/5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.
Period Title: Overall Study
Started	349	349
Completed	325	331
Not Completed	24	18
Reason Not Completed
Adverse Event	10	8
Withdrawal by Subject	7	5
Lost to Follow-up	2	3
Protocol Violation	3	1
Subject no longer requires study drug	0	1
Abnormal laboratory value(s)	1	0
Lack of Efficacy	1	0

Baseline Characteristics

Arm/Group Title		Valsartan/Amlodipine 80/5 mg	Amlodipine 5 mg	Total
Arm/Group Description		1 valsartan/amlodipine 80/5 mg tablet and 1 placebo capsule matching amlodipine 5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.	1 amlodipine 5 mg capsule and 1 placebo tablet matching valsartan/amlodipine 80/5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.	Total of all reporting groups
Overall Number of Baseline Participants		347	349	696
Baseline Analysis Population Description		[Not Specified]
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	347 participants	349 participants	696 participants
		53.4 (9.7)	54.2 (9.1)	53.8 (9.4)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	347 participants	349 participants	696 participants
	Female	134 38.6%	109 31.2%	243 34.9%
	Male	213 61.4%	240 68.8%	453 65.1%

Outcome Measures

1. Primary Outcome

Title	Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study (Week 8)
Description	Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated. A negative change score indicates lowered BP.
Time Frame	Baseline to end of study (Week 8)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT): All randomized patients who had baseline and at least one post-baseline efficacy measurement, ie, any post-baseline measurement of primary or secondary efficacy variables. For patients who did not complete the Week 8 assessment, a last observation carried forward (LOCF) approach was used.

Arm/Group Title	Valsartan/Amlodipine 80/5 mg	Amlodipine 5 mg
Arm/Group Description:	1 valsartan/amlodipine 80/5 mg tablet and 1 placebo capsule matching amlodipine 5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.	1 amlodipine 5 mg capsule and 1 placebo tablet matching valsartan/amlodipine 80/5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.
Overall Number of Participants Analyzed	347	349
Least Squares Mean (Standard Error); Unit of Measure: mmHg
	-9.7 (0.42)	-7.1 (0.42)

2. Secondary Outcome

Title	Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to End of Study (Week 8)
Description	Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated. A negative change score indicates lowered BP.
Time Frame	Baseline to end of study (Week 8)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT): All randomized patients who had baseline and at least one post-baseline efficacy measurement, ie, any post-baseline measurement of primary or secondary efficacy variables. For patients who did not complete the Week 8 assessment, a last observation carried forward (LOCF) approach was used.

Arm/Group Title	Valsartan/Amlodipine 80/5 mg	Amlodipine 5 mg
Arm/Group Description:	1 valsartan/amlodipine 80/5 mg tablet and 1 placebo capsule matching amlodipine 5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.	1 amlodipine 5 mg capsule and 1 placebo tablet matching valsartan/amlodipine 80/5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.
Overall Number of Participants Analyzed	347	349
Least Squares Mean (Standard Error); Unit of Measure: mmHg
	-11.4 (0.61)	-7.4 (0.60)

3. Secondary Outcome

Title	Percentage of Patients Achieving a Diastolic Response at the End of the Study (Week 8)
Description	A patient achieved a diastolic response if their msDBP < 90 mmHg at Week 8 or they had a ≥ 10 mmHg decrease in msDBP compared to baseline at the end of the study (Week 8). Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated.
Time Frame	Baseline to end of study (Week 8)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT): All randomized patients who had baseline and at least one post-baseline efficacy measurement, ie, any post-baseline measurement of primary or secondary efficacy variables. For patients who did not complete the Week 8 assessment, a last observation carried forward (LOCF) approach was used.

Arm/Group Title	Valsartan/Amlodipine 80/5 mg	Amlodipine 5 mg
Arm/Group Description:	1 valsartan/amlodipine 80/5 mg tablet and 1 placebo capsule matching amlodipine 5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.	1 amlodipine 5 mg capsule and 1 placebo tablet matching valsartan/amlodipine 80/5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.
Overall Number of Participants Analyzed	347	349
Measure Type: Number; Unit of Measure: Percentage of patients
	79.3	66.8

4. Secondary Outcome

Title	Percentage of Patients Achieving Diastolic Control at the End of the Study (Week 8)
Description	A patient achieved diastolic control if their msDBP < 90 mmHg at the end of the study (Week 8). Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated.
Time Frame	Baseline to end of study (Week 8)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT): All randomized patients who had baseline and at least one post-baseline efficacy measurement, ie, any post-baseline measurement of primary or secondary efficacy variables. For patients who did not complete the Week 8 assessment, a last observation carried forward (LOCF) approach was used.

Arm/Group Title	Valsartan/Amlodipine 80/5 mg	Amlodipine 5 mg
Arm/Group Description:	1 valsartan/amlodipine 80/5 mg tablet and 1 placebo capsule matching amlodipine 5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.	1 amlodipine 5 mg capsule and 1 placebo tablet matching valsartan/amlodipine 80/5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.
Overall Number of Participants Analyzed	347	349
Measure Type: Number; Unit of Measure: Percentage of patients
	75.5	64.5

5. Secondary Outcome

Title	Percentage of Patients Achieving Overall Control at the End of the Study (Week 8)
Description	A patient achieved overall control if the msSBP/msDBP < 140/90 mmHg at the end of the study (Week 8). Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated.
Time Frame	Baseline to end of study (Week 8)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT): All randomized patients who had baseline and at least one post-baseline efficacy measurement, ie, any post-baseline measurement of primary or secondary efficacy variables. For patients who did not complete the Week 8 assessment, a last observation carried forward (LOCF) approach was used.

Arm/Group Title	Valsartan/Amlodipine 80/5 mg	Amlodipine 5 mg
Arm/Group Description:	1 valsartan/amlodipine 80/5 mg tablet and 1 placebo capsule matching amlodipine 5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.	1 amlodipine 5 mg capsule and 1 placebo tablet matching valsartan/amlodipine 80/5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.
Overall Number of Participants Analyzed	347	349
Measure Type: Number; Unit of Measure: Percentage of patients
	69.2	57.6

6. Secondary Outcome

Title	Change in 24-hour Mean Ambulatory Diastolic and Systolic BP From Baseline at the End of the Study (Week 8)
Description	Two 24 hour ambulatory blood pressure monitoring (ABPM) evaluations were performed, one at baseline prior to randomization and one at Week 8 (end of study), in a subset of the intent-to-treat population of patients. For each evaluation, the ABPM device was attached to the non-dominant arm of the patient. A correlation was made between the ABPM device readings and measurements taken with a mercury sphygmomanometer and stethoscope. Following the correlation procedure, BP was measured at study specified intervals. A negative change score indicates lowered BP.
Time Frame	Baseline to end of study (Week 8)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Valsartan/Amlodipine 80/5 mg	Amlodipine 5 mg
Arm/Group Description:	1 valsartan/amlodipine 80/5 mg tablet and 1 placebo capsule matching amlodipine 5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.	1 amlodipine 5 mg capsule and 1 placebo tablet matching valsartan/amlodipine 80/5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.
Overall Number of Participants Analyzed	41	41
Mean (Standard Deviation); Unit of Measure: mmHg
Diastolic BP	-6.3 (5.85)	0.3 (5.82)
Systolic BP	-7.3 (7.62)	-0.2 (8.64)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Valsartan/Amlodipine 80/5 mg	Amlodipine 5 mg
Arm/Group Description	1 valsartan/amlodipine 80/5 mg tablet and 1 placebo capsule matching amlodipine 5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.	1 amlodipine 5 mg capsule and 1 placebo tablet matching valsartan/amlodipine 80/5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.
All-Cause Mortality
	Valsartan/Amlodipine 80/5 mg	Amlodipine 5 mg
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Valsartan/Amlodipine 80/5 mg	Amlodipine 5 mg
	Affected / at Risk (%)	Affected / at Risk (%)
Total	4/349 (1.15%)	2/349 (0.57%)
Gastrointestinal disorders
Gastric ulcer † 1	1/349 (0.29%)	1/349 (0.29%)
Injury, poisoning and procedural complications
Humerus fracture † 1	1/349 (0.29%)	0/349 (0.00%)
Musculoskeletal and connective tissue disorders
Jaw cyst † 1	1/349 (0.29%)	0/349 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Parathyroid tumour benign † 1	0/349 (0.00%)	1/349 (0.29%)
Nervous system disorders
Post herpetic neuralgia † 1	1/349 (0.29%)	0/349 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Valsartan/Amlodipine 80/5 mg	Amlodipine 5 mg
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/349 (0.00%)	0/349 (0.00%)

Limitations and 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.

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.

Results Point of Contact

• Name/Title: Study Director
• Organization: Novartis Pharmaceuticals
• Phone: 862 778-8300

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ke Y, Zhu D, Hong H, Zhu J, Wang R, Cardenas P, Zhang Y. Efficacy and safety of a single-pill combination of amlodipine/valsartan in Asian hypertensive patients inadequately controlled with amlodipine monotherapy. Curr Med Res Opin. 2010 Jul;26(7):1705-13. doi: 10.1185/03007995.2010.487391.

• Responsible Party: Novartis Medical Director, Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00413049 History of Changes
• Other Study ID Numbers: CVAA489A2315
• First Submitted: December 18, 2006
• First Posted: December 19, 2006
• Results First Submitted: January 11, 2011
• Results First Posted: February 8, 2011
• Last Update Posted: April 29, 2011