Trial Outcomes & Findings for To Demonstrate Non-inferiority of Combination of 5 mg Amlodipine/ 80 mg Valsartan to 160 mg Valsartan Alone (NCT NCT01070043)

NCT ID: NCT01070043

Last Updated: 2011-10-19

Results Overview

Two arterial blood pressure (BP) determinations were made after the participant was in the sitting position for 5 minutes according to the American Heart Association guidelines using a calibrated standard aneroid or mercury sphygmomanometer or a calibrated standard sphygmomanometer. The change in mean sitting systolic blood pressure (msSBP) was calculated comparing the Week 8 readings to the readings taken at baseline.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 60 participants
• Primary outcome timeframe: Baseline and 8 weeks
• Results posted on: 2011-10-19

Participant Flow

A 4 week run-in phase preceded the randomized, double-blind treatment phase of the study. During the run-in phase, participants took valsartan 80 mg daily before a meal. Sixty participants entered the run-in phase. Those participants who met the inclusion criteria entered the randomized, double-blind treatment phase.

Participant milestones

Measure	Run-In Valsartan 80 mg During run-in period, oral valsartan 80 mg once daily for 4 weeks.	Amlodipine 5 mg/Valsartan 80 mg During double-blind treatment period, patients randomized to combination therapy received daily one dosage (Amlodipine/Valsartan 5mg/80mg) with one single tablet size for 8 weeks.	Valsartan 160 mg In double blinded treatment period, patients randomized to this arm received 160 mg Valsartan once daily for 8 weeks.
Run-In Phase STARTED	60	0	0
Run-In Phase COMPLETED	42	0	0
Run-In Phase NOT COMPLETED	18	0	0
Double-Blind Treatment STARTED	0	21	21
Double-Blind Treatment COMPLETED	0	21	19
Double-Blind Treatment NOT COMPLETED	0	0	2

Reasons for withdrawal

Measure	Run-In Valsartan 80 mg During run-in period, oral valsartan 80 mg once daily for 4 weeks.	Amlodipine 5 mg/Valsartan 80 mg During double-blind treatment period, patients randomized to combination therapy received daily one dosage (Amlodipine/Valsartan 5mg/80mg) with one single tablet size for 8 weeks.	Valsartan 160 mg In double blinded treatment period, patients randomized to this arm received 160 mg Valsartan once daily for 8 weeks.
Run-In Phase Did not Meet Inclusion Criteria	18	0	0
Double-Blind Treatment Adverse Event	0	0	2

Baseline Characteristics

To Demonstrate Non-inferiority of Combination of 5 mg Amlodipine/ 80 mg Valsartan to 160 mg Valsartan Alone

Baseline characteristics by cohort

Measure	Amlodipine 5mg/Valsartan 80 mg n=21 Participants During double-blind treatment period, patients randomized to combination therapy received daily one dosage (Amlodipine/Valsartan 5mg/80mg) with one single tablet size for 8 weeks.	Valsartan 160 mg n=21 Participants In double blinded treatment period, patients randomized to this arm received 160 mg Valsartan once daily for 8 weeks.	Total n=42 Participants Total of all reporting groups
Age Continuous	59.50 years STANDARD_DEVIATION 13.81 • n=5 Participants	55.13 years STANDARD_DEVIATION 11.81 • n=7 Participants	57.31 years STANDARD_DEVIATION 13.81 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	13 Participants n=7 Participants	25 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 8 weeks

Population: The Intent-to-Treat (ITT) Population includes all participants having taken at least one dose of study medication.

Two arterial blood pressure (BP) determinations were made after the participant was in the sitting position for 5 minutes according to the American Heart Association guidelines using a calibrated standard aneroid or mercury sphygmomanometer or a calibrated standard sphygmomanometer. The change in mean sitting systolic blood pressure (msSBP) was calculated comparing the Week 8 readings to the readings taken at baseline.

Outcome measures

Measure	Amlodipine 5 mg/Valsartan 80 mg n=21 Participants During double-blind treatment period, patients randomized to combination therapy received daily one dosage (Amlodipine/Valsartan 5mg/80mg) with one single tablet size for 8 weeks.	Valsartan 160 mg n=21 Participants In double blinded treatment period, patients randomized to this arm received 160 mg Valsartan once daily for 8 weeks.
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) From Office Blood Pressure Measurement Baseline	150.26 mmHg Standard Deviation 12.91	141.14 mmHg Standard Deviation 12.71
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) From Office Blood Pressure Measurement 8 weeks	133.79 mmHg Standard Deviation 14.63	133.68 mmHg Standard Deviation 12.73
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) From Office Blood Pressure Measurement Change from baseline to 8 weeks	-16.48 mmHg Standard Deviation 15.53	-7.23 mmHg Standard Deviation 11.60

PRIMARY outcome

Timeframe: Baseline and 8 weeks

Population: The Intent-to-Treat (ITT) Population includes all participants having taken at least one dose of study medication.

Two arterial blood pressure (BP) determinations were made after the participant was in the sitting position for 5 minutes according to the American Heart Association guidelines using a calibrated standard aneroid or mercury sphygmomanometer or a calibrated standard sphygmomanometer. The change in mean sitting diastolic blood pressure (msDBP) was calculated comparing the Week 8 readings to the readings taken at Baseline.

Outcome measures

Measure	Amlodipine 5 mg/Valsartan 80 mg n=21 Participants During double-blind treatment period, patients randomized to combination therapy received daily one dosage (Amlodipine/Valsartan 5mg/80mg) with one single tablet size for 8 weeks.	Valsartan 160 mg n=21 Participants In double blinded treatment period, patients randomized to this arm received 160 mg Valsartan once daily for 8 weeks.
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) From Office Blood Pressure Measurement Baseline	92.12 mmHg Standard Deviation 10.84	89.98 mmHg Standard Deviation 9.37
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) From Office Blood Pressure Measurement 8 weeks	82.29 mmHg Standard Deviation 8.74	86.73 mmHg Standard Deviation 9.10
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) From Office Blood Pressure Measurement Change from baseline to 8 weeks	-9.83 mmHg Standard Deviation 7.66	-2.65 mmHg Standard Deviation 6.75

SECONDARY outcome

Timeframe: Baseline and 8 weeks

Population: The Intent-to-Treat (ITT) Population includes all participants having taken at least one dose of study medication.

Validated automated ambulatory blood pressure monitors were dispensed to participants with instructions on correct use. Automated blood pressure readings were obtained every 15-30 minutes during waking hours and every 30-60 minutes during sleep for a total of 24 hours. The change in mean systolic blood pressure (mSBP) over 24 hours was measured from baseline to 8 weeks of treatment during the double-blind phase.

Outcome measures

Measure	Amlodipine 5 mg/Valsartan 80 mg n=21 Participants During double-blind treatment period, patients randomized to combination therapy received daily one dosage (Amlodipine/Valsartan 5mg/80mg) with one single tablet size for 8 weeks.	Valsartan 160 mg n=21 Participants In double blinded treatment period, patients randomized to this arm received 160 mg Valsartan once daily for 8 weeks.
Change From Baseline in Mean Systolic Blood Pressure (mSBP) From Ambulatory Blood Pressure Measurement (ABPM) Over 24 Hours Baseline	144.38 mmHg Standard Deviation 17.39	139.76 mmHg Standard Deviation 13.46
Change From Baseline in Mean Systolic Blood Pressure (mSBP) From Ambulatory Blood Pressure Measurement (ABPM) Over 24 Hours 8 weeks	129.67 mmHg Standard Deviation 14.03	131.11 mmHg Standard Deviation 12.39
Change From Baseline in Mean Systolic Blood Pressure (mSBP) From Ambulatory Blood Pressure Measurement (ABPM) Over 24 Hours Change from baseline to 8 weeks	-14.71 mmHg Standard Deviation 11.64	-6.39 mmHg Standard Deviation 12.06

SECONDARY outcome

Timeframe: Baseline and 8 weeks

Population: The Intent-to-Treat (ITT) Population includes all participants having taken at least one dose of study medication.

Validated automated ambulatory blood pressure monitors were dispensed to participants with instructions on correct use. Automated blood pressure readings were obtained every 15-30 minutes during waking hours and every 30-60 minutes during sleep for a total of 24 hours. The change in mean diastolic blood pressure (mDBP) over 24 hours was measured from baseline to 8 weeks of treatment during the double-blind.

Outcome measures

Measure	Amlodipine 5 mg/Valsartan 80 mg n=21 Participants During double-blind treatment period, patients randomized to combination therapy received daily one dosage (Amlodipine/Valsartan 5mg/80mg) with one single tablet size for 8 weeks.	Valsartan 160 mg n=21 Participants In double blinded treatment period, patients randomized to this arm received 160 mg Valsartan once daily for 8 weeks.
Change From Baseline in Mean Diastolic Blood Pressure (mDBP) From Ambulatory Blood Pressure Measurement (ABPM) Over 24 Hours After 8 Weeks of Treatment During the Double-blind Phase Baseline	86.95 mmHg Standard Deviation 14.14	87.90 mmHg Standard Deviation 9.44
Change From Baseline in Mean Diastolic Blood Pressure (mDBP) From Ambulatory Blood Pressure Measurement (ABPM) Over 24 Hours After 8 Weeks of Treatment During the Double-blind Phase 8 weeks	79.29 mmHg Standard Deviation 10.70	82.94 mmHg Standard Deviation 8.42
Change From Baseline in Mean Diastolic Blood Pressure (mDBP) From Ambulatory Blood Pressure Measurement (ABPM) Over 24 Hours After 8 Weeks of Treatment During the Double-blind Phase Change from baseline to 8 weeks	-7.67 mmHg Standard Deviation 7.43	-3.56 mmHg Standard Deviation 7.70

SECONDARY outcome

Timeframe: 8 weeks

Population: Safety population included all patients who received at least one study medication during the study period.

Outcome measures

Measure	Amlodipine 5 mg/Valsartan 80 mg n=21 Participants During double-blind treatment period, patients randomized to combination therapy received daily one dosage (Amlodipine/Valsartan 5mg/80mg) with one single tablet size for 8 weeks.	Valsartan 160 mg n=21 Participants In double blinded treatment period, patients randomized to this arm received 160 mg Valsartan once daily for 8 weeks.
Number of Participants With Adverse Events During Double-blind Phase Total AE	9 Participants	15 Participants
Number of Participants With Adverse Events During Double-blind Phase At least one AE	7 Participants	11 Participants
Number of Participants With Adverse Events During Double-blind Phase AE Not related to drug	9 Participants	15 Participants

Adverse Events

Amlodipine 5 mg/Valsartan 80 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Valsartan 160 mg

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Measure	Amlodipine 5 mg/Valsartan 80 mg n=21 participants at risk During double-blind treatment period, patients randomized to combination therapy received daily one dosage (Amlodipine/Valsartan 5mg/80mg) with one single tablet size for 8 weeks.	Valsartan 160 mg n=21 participants at risk In double blinded treatment period, patients randomized to this arm received 160 mg Valsartan once daily for 8 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/21 All patients who received at least one study medication during the double-blinded study period were included in the reported safety population.	4.8% 1/21 All patients who received at least one study medication during the double-blinded study period were included in the reported safety population.

Other adverse events

Measure	Amlodipine 5 mg/Valsartan 80 mg n=21 participants at risk During double-blind treatment period, patients randomized to combination therapy received daily one dosage (Amlodipine/Valsartan 5mg/80mg) with one single tablet size for 8 weeks.	Valsartan 160 mg n=21 participants at risk In double blinded treatment period, patients randomized to this arm received 160 mg Valsartan once daily for 8 weeks.
Infections and infestations Upper respiratory tract infection	9.5% 2/21 All patients who received at least one study medication during the double-blinded study period were included in the reported safety population.	14.3% 3/21 All patients who received at least one study medication during the double-blinded study period were included in the reported safety population.
Nervous system disorders Dizziness	0.00% 0/21 All patients who received at least one study medication during the double-blinded study period were included in the reported safety population.	9.5% 2/21 All patients who received at least one study medication during the double-blinded study period were included in the reported safety population.
Nervous system disorders Headache	9.5% 2/21 All patients who received at least one study medication during the double-blinded study period were included in the reported safety population.	4.8% 1/21 All patients who received at least one study medication during the double-blinded study period were included in the reported safety population.
Respiratory, thoracic and mediastinal disorders Cough	9.5% 2/21 All patients who received at least one study medication during the double-blinded study period were included in the reported safety population.	9.5% 2/21 All patients who received at least one study medication during the double-blinded study period were included in the reported safety population.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862 - 778- 8300

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER