Efficacy and Safety of Valsartan and Amlodipine in Patien... | NCT00425373

NCT00425373

Status Module

Label	Type	Intervention Names
Valsartan + amlodipine 40/2.5 mg	Experimental	Drug: Valsartan + amlodipine 40/2.5 mg
Valsartan + amlodipine 40/5 mg	Experimental	Drug: Valsartan + amlodipine 40/5 mg
Valsartan + amlodipine 80/2.5 mg	Experimental	Drug: Valsartan + amlodipine 80/2.5 mg
Valsartan + amlodipine 80/5 mg	Experimental	Drug: Valsartan + amlodipine 80/5 mg
Valsartan 40 mg	Active Comparator	Drug: Valsartan 40 mg
Valsartan 80 mg	Active Comparator	Drug: Valsartan 80 mg
Amlodipine 2.5 mg	Active Comparator	Drug: Amlodipine 2.5 mg

Name	Type	Description	Arm Group Labels	Other Names
Valsartan + amlodipine 40/2.5 mg	Drug	Valsartan + amlodipine 40/2.5 mg tablet plus 3 tablet and 2 capsule placebos taken once daily	Valsartan + amlodipine 40/2.5 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in Mean Sitting Diastolic Blood Pressure (MSDBP) From Baseline to End of Study (Week 8)	At study entry, blood pressure was measured in both arms using a standard method described in the protocol. The arm with the higher diastolic BP reading was used for the measurements at all subsequent visits. Blood pressure in the sitting position was measured after resting in a seated position for at least 5 minutes. The measurement was repeated a total of 3 times at intervals of 1 to 2 minutes. A negative number indicates lowered blood pressure.	Baseline to end of study (Week 8)

Secondary Outcomes

Measure	Description	Time Frame
Change in Mean Sitting Systolic Blood Pressure (MSSBP) From Baseline to End of Study (Week 8)	At study entry, blood pressure was measured in both arms using a standard method described in the protocol. The arm with the higher diastolic BP reading was used for the measurements at all subsequent visits. Blood pressure in the sitting position was measured after resting in a seated position for at least 5 minutes. The measurement was repeated a total of 3 times at intervals of 1 to 2 minutes. A negative number indicates lowered blood pressure.

Eligibility Module

Eligibility Criteria

Inclusion criteria

Patients with essential hypertension measured by electronic hemodynamometer. - - Patients must satisfy the following criteria.
1. MSDBP <110 mmHg and MSSBP <180 mmHg at Visit 1
2. MSDBP ≥ 90 mmHg and < 110 mmHg and MSSBP < 180 mmHg at Visit 2
3. MSDBP ≥ 95 mmHg and < 110 mmHg and MSSBP < 180 mmHg at Visit 3
4. The absolute difference in MSDBP between Visit 2 and 3 is ≤ 10 mmHg
Male or female outpatients.
Aged => 20 and =< 80 years (at the time of signing informed consent).
Patients who have written informed consent to participate in this study.

Exclusion criteria

Pregnant women, nursing (lactating) mothers, women suspected of being pregnant, or women who wish to be pregnant during the study, women of child-bearing potential.
Patients with secondary hypertension or suspected of having secondary hypertension.
Patients with a history of malignant hypertension.
Patients with an inability to completely discontinue all prior antihypertensive medications safely for a period of 12 weeks as required by the protocol.
Patients with or with a history of any of the following diseases or signs: Cardiac disease, renal disease, cerebrovascular disorder
Patients with a clinically significant allergy (asthma on pharmacotherapy, multi-drug allergy, or drug-induced or food-induced anaphylactic reactions).
Patients hypersensitive to AII receptor antagonists, calcium channel blockers or dihydropyridine derivatives.
Known moderate or malignant retinopathy.
Patients with or with a history of pancreatitis. Patients with pancreatic injury, or evidence of impaired pancreatic function/injury within 12 months of Visit 1.
Patients with any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of any drug.
Patients with volume depletion based on the investigator's or subinvestigator's clinical judgment using vital signs, skin turgor, moistness of mucous membrane and laboratory values.
Patients who are found to have low Na and K (Na <130 mEq/L, K <3.3mEq/L) or high in these parameters (Na ≥ 152 mEq/L, K ≥ 5.2 mEq/L) by laboratory tests at Visit 1.
Patients with type I diabetes mellitus on treatment with insulin, or patients with type II diabetes with poor glucose control defined as a glycosylated hemoglobin (HbA1c) > 8.0% at Visit 1.
Patients with or with a history of malignant tumors including leukemia and lymphoma, treated or untreated, within the past 5 years of Visit 1 whether or not there is evidence of local recurrence or metastases (except for localized basal cell carcinoma of the skin).
Patients with any severe, life-threatening disease within the past 5 years. Patients with a history of autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus.
Any surgical or medical condition, which in the opinion of the investigator or subinvestigator, place the patient at higher risk from his/her participation in the study, or are likely to prevent the patient from complying with the requirement of the study or completing the trial period.
Patients who have with or with a history of drug or alcohol abuse within the last 2 years of Visit 1. Patients who have received other investigational product within 12 weeks of Visit 1.
Any chronic inflammatory condition needing chronic anti-inflammatory drug therapy.
Persons directly involved in the execution of this study.
Patients who are considered unlikely to comply with the requirements specified in the protocol by the investigator or subinvestigator.

Name	Affiliation	Role
Novartis Japan	Sponsor GmbH	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Pharmaceuticals		Tokyo		11111	Japan

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Valsartan + Amlodipine 40/2.5 mg	Valsartan + amlodipine 40/2.5 mg tablet plus 3 tablet and 2 capsule placebos taken once daily
FG001	Valsartan + Amlodipine 40/5 mg	Valsartan + amlodipine 40/5mg tablet plus 3 tablet and 2 capsule placebos taken once daily

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Valsartan + Amlodipine 40/2.5 mg	Valsartan + amlodipine 40/2.5 mg tablet plus 3 tablet and 2 capsule placebos taken once daily
BG001	Valsartan + Amlodipine 40/5 mg	Valsartan + amlodipine 40/5mg tablet plus 3 tablet and 2 capsule placebos taken once daily
BG002	Valsartan + Amlodipine 80/2.5 mg	Valsartan + amlodipine 80/2.5 mg tablet plus 3 tablet and 2 capsule placebos taken once daily
BG003	Valsartan + Amlodipine 80/5 mg	Valsartan + amlodipine 80/5mg tablet plus 3 tablet and 2 capsule placebos taken once daily
BG004	Valsartan 40 mg	Valsartan 40 mg tablet plus 3 tablet and 2 capsule placebos taken once daily
BG005	Valsartan 80 mg	Valsartan 80 mg tablet plus 3 tablet and 2 capsule placebos taken once daily
BG006	Amlodipine 2.5 mg	Amlodipine 2.5 mg capsule plus 4 tablet and 1 capsule placebos taken once daily
BG007	Amlodipine 5 mg	Amlodipine 5 mg capsule plus 4 tablet and 1 capsule placebos taken once daily
BG008	Placebo	4 tablet and 2 capsule placebos taken once daily
BG009	Total	Total of all reporting groups

Units	Counts
Participants	BG000159 BG001167 BG002160 BG003162 BG004169 BG005163 BG006161 BG007161 BG008166 BG0091468

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change in Mean Sitting Diastolic Blood Pressure (MSDBP) From Baseline to End of Study (Week 8)

At study entry, blood pressure was measured in both arms using a standard method described in the protocol. The arm with the higher diastolic BP reading was used for the measurements at all subsequent visits. Blood pressure in the sitting position was measured after resting in a seated position for at least 5 minutes. The measurement was repeated a total of 3 times at intervals of 1 to 2 minutes. A negative number indicates lowered blood pressure.

Intent-to-treat (ITT): All randomized patients who had a baseline and at least one post-baseline assessment of the variable analyzed. Baseline is the Week 0 value and end of study is the value at Week 8 or the last observation carried forward (LOCF) value.

Posted

Least Squares Mean

Standard Error

mm Hg

Baseline to end of study (Week 8)

ID	Title	Description
OG000	Valsartan + Amlodipine 40/2.5 mg	Valsartan + amlodipine 40/2.5 mg tablet plus 3 tablet and 2 capsule placebos taken once daily
OG001	Valsartan + Amlodipine 40/5 mg	Valsartan + amlodipine 40/5mg tablet plus 3 tablet and 2 capsule placebos taken once daily
OG002	Valsartan + Amlodipine 80/2.5 mg	Valsartan + amlodipine 80/2.5 mg tablet plus 3 tablet and 2 capsule placebos taken once daily
OG003	Valsartan + Amlodipine 80/5 mg	Valsartan + amlodipine 80/5mg tablet plus 3 tablet and 2 capsule placebos taken once daily
OG004	Valsartan 40 mg	Valsartan 40 mg tablet plus 3 tablet and 2 capsule placebos taken once daily
OG005	Valsartan 80 mg	Valsartan 80 mg tablet plus 3 tablet and 2 capsule placebos taken once daily
OG006	Amlodipine 2.5 mg	Amlodipine 2.5 mg capsule plus 4 tablet and 1 capsule placebos taken once daily
OG007	Amlodipine 5 mg	Amlodipine 5 mg capsule plus 4 tablet and 1 capsule placebos taken once daily
OG008	Placebo	4 tablet and 2 capsule placebos taken once daily

Units	Counts
Participants	OG000159 OG001167 OG002160 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-13.5± 0.62 OG001-16.5± 0.60 OG002-12.6± 0.62 OG003

Secondary

Change in Mean Sitting Systolic Blood Pressure (MSSBP) From Baseline to End of Study (Week 8)

Posted

Least Squares Mean

Standard Error

mm Hg

Baseline to end of study (Week 8)

ID	Title	Description
OG000	Valsartan + Amlodipine 40/2.5 mg	Valsartan + amlodipine 40/2.5 mg tablet plus 3 tablet and 2 capsule placebos taken once daily
OG001	Valsartan + Amlodipine 40/5 mg	Valsartan + amlodipine 40/5mg tablet plus 3 tablet and 2 capsule placebos taken once daily
OG002	Valsartan + Amlodipine 80/2.5 mg

Secondary

Percentage of Patients Achieving MSDBP < 90 mmHg or a => 10 mm Hg Decrease Compared to Baseline at the End of the Study (Week 8)

Posted

Number

Percentage of patients

Baseline to end of study (Week 8)

ID	Title	Description
OG000	Valsartan + Amlodipine 40/2.5 mg	Valsartan + amlodipine 40/2.5 mg tablet plus 3 tablet and 2 capsule placebos taken once daily
OG001	Valsartan + Amlodipine 40/5 mg	Valsartan + amlodipine 40/5mg tablet plus 3 tablet and 2 capsule placebos taken once daily
OG002	Valsartan + Amlodipine 80/2.5 mg

Secondary

Percentage of Patients Achieving MSDBP < 90mmHg at the End of the Study (Week 8)

Posted

Number

Percentage of patients

Baseline to end of study (Week 8)

ID	Title	Description
OG000	Valsartan + Amlodipine 40/2.5 mg	Valsartan + amlodipine 40/2.5 mg tablet plus 3 tablet and 2 capsule placebos taken once daily
OG001	Valsartan + Amlodipine 40/5 mg	Valsartan + amlodipine 40/5mg tablet plus 3 tablet and 2 capsule placebos taken once daily
OG002	Valsartan + Amlodipine 80/2.5 mg	Valsartan + amlodipine 80/2.5 mg tablet plus 3 tablet and 2 capsule placebos taken once daily

Secondary

Percentage of Patients Achieving MSDBP < 90 mm Hg and MSSBP < 140 mm Hg at the End of the Study (Week 8)

Posted

Number

Percentage of patients

Baseline to end of study (Week 8)

ID	Title	Description
OG000	Valsartan + Amlodipine 40/2.5 mg	Valsartan + amlodipine 40/2.5 mg tablet plus 3 tablet and 2 capsule placebos taken once daily
OG001	Valsartan + Amlodipine 40/5 mg	Valsartan + amlodipine 40/5mg tablet plus 3 tablet and 2 capsule placebos taken once daily
OG002	Valsartan + Amlodipine 80/2.5 mg

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	4 tablet and 2 capsule placebos taken once daily	2	166	17	166
EG001	Valsartan 40 mg	Valsartan 40 mg tablet plus 3 tablet and 2 capsule placebos taken once daily	0	169	23	169
EG002	Valsartan 80 mg	Valsartan 80 mg tablet plus 3 tablet and 2 capsule placebos taken once daily	0	163	19	163
EG003	Amlodipine 2.5 mg	Amlodipine 2.5 mg capsule plus 4 tablet and 1 capsule placebos taken once daily	1	161	12	161
EG004	Valsartan + Amlodipine 40/2.5 mg	Valsartan + amlodipine 40/2.5 mg tablet plus 3 tablet and 2 capsule placebos taken once daily	0	159	17	159
EG005	Valsartan + Amlodipine 80/2.5 mg	Valsartan + amlodipine 80/2.5 mg tablet plus 3 tablet and 2 capsule placebos taken once daily	1	160	9	160
EG006	Amlodipine 5 mg	Amlodipine 2.5 mg 2 capsules plus 4 tablet placebos taken once daily	0	161	12	161
EG007	Valsartan + Amlodipine 40/5 mg	Valsartan + amlodipine 40/5mg tablet plus 3 tablet and 2 capsule placebos taken once daily	1	167	20	167
EG008	Valsartan + Amlodipine 80/5 mg	Valsartan + amlodipine 80/5mg tablet plus 3 tablet and 2 capsule placebos taken once daily	0	162	14	162

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Supraventricular tachycardia	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected166 at risk EG0010 affected169 at risk EG0020 affected163 at risk EG0031 affected161 at risk EG0040 affected159 at risk EG0050 affected160 at risk EG0060 affected161 at risk EG0070 affected167 at risk EG0080 affected162 at risk
Ulcerative keratitis	Eye disorders	MedDRA	Systematic Assessment	EG0001 affected166 at risk EG0010 affected169 at risk EG0020 affected163 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected166 at risk EG0010 affected169 at risk EG0020 affected163 at risk EG003
Pyelonephritis acute	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected166 at risk EG0010 affected169 at risk EG0020 affected163 at risk EG003
Compression fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected166 at risk EG0010 affected169 at risk EG0020 affected163 at risk EG003

ID	Term
D000075222	Essential Hypertension
D006973	Hypertension

ID	Term
D014652	Vascular Diseases
D002318	Cardiovascular Diseases

ID	Term
D013777	Tetrazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D014633	Valine
D000597	Amino Acids, Branched-Chain
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins
D000601	Amino Acids, Essential
D004095	Dihydropyridines
D011725	Pyridines