Efficacy/Safety of Valsartan Plus Amlodipine and Amlodipine Alone in Patients With Hypertension
Condition: Hypertension
MeSH terms: Hypertension
Intervention: Valsartan/amlodipine 80/5 mg; Amlodipine 5 mg
Intervention 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.
Intervention MeSH terms: Amlodipine; Valsartan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 698.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Hypertension, valsartan, amlodipine, high blood pressure

Summary:

      This study will evaluate the safety and efficacy of the fixed combination of
      valsartan/amlodipine in adult patients with mild to moderate hypertension
    

Eligibility criteria:

        Inclusion criteria

          -  Male or female outpatients ≥ 18 years and < 86 years

          -  Patients with essential hypertension measured by calibrated mercury sphygmomanometer
             (preferred) or an aneroid device if a mercury sphygmomanometer was not available.

          -  At Visit 1, patients not treated with antihypertensive medications had to have a MSDBP
             of ≥ 95 mmHg and < 110 mmHg; those patients treated with antihypertensive medication
             had to have a MSDBP of < 110 mmHg.

          -  At Visit 2, patients must have a MSDBP of ≥ 95 mmHg but < 110 mmHg.

          -  At Visit 3, patients must have a MSDBP of ≥ 90 mmHg and < 110 mmHg.

          -  Patients who were eligible and able to participate in the study, and who consented to
             do so after the purpose and nature of the investigation had been clearly explained to
             them (written informed consent).

        Exclusion criteria

          -  Severe hypertension (MSDBP ≥ 110 mmHg and/or MSSBP ≥ 180 mmHg).

          -  In cases where the patient was on more than one antihypertensive drug whether in fixed
             or free combination, the investigator considered the efficacy and strength of each
             active ingredient in order to determine if the patient could be safely removed from
             their antihypertensive treatment.

          -  Known or suspected contraindications, including history of allergy or hypersensitivity
             to angiotensin receptor blockers (ARB), calcium channel blockers (CCB), or to drugs
             with similar chemical structures.

          -  Administration of any agent indicated for the treatment of hypertension after Visit 1
             with the exception of those agents that required tapering down.

          -  Inability to discontinue all prior antihypertensive medications safely for a maximum
             period of up to 28 days prior to Visit 2, as required by the protocol.

          -  History of hypertensive encephalopathy, cerebrovascular accident or transient ischemic
             attack, myocardial infarction or all types of revascularization.

          -  Malignant hypertension.

          -  All patients with Type 1 diabetes mellitus and those patients with Type 2 diabetes
             mellitus who were not well controlled based on the investigator's clinical judgment.
             Patients being treated for diabetes mellitus had to have satisfactory metabolic
             control. Type 2 diabetic patients taking oral anti-diabetic medication had to be on a
             stable dose for at least 4 weeks prior to Visit 1.

          -  Pregnant or nursing (lactating) women, where pregnancy was defined as the state of a
             female after conception and until the termination of gestation, confirmed by a
             positive human chorionic gonadotropin (hCG) laboratory test (> 5 mIU/ml).

          -  Women of child-bearing potential (WOCBP), defined as all women physiologically capable
             of becoming pregnant, including women whose career, lifestyle, or sexual orientation
             precluded intercourse with a male partner and women whose partners had been sterilized
             by vasectomy or other means, UNLESS they met the following definition of
             post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of
             spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels > 40 mIU/m
             or 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy OR were
             using one or more of the following acceptable methods of contraception: surgical
             sterilization (e.g., bilateral tubal ligation, vasectomy), and double-barrier methods
             (any double combination of: intra-uterine device [IUD], male or female condom with
             spermicidal gel, diaphragm, sponge, cervical cap). Acceptable methods of contraception
             included total abstinence at the discretion of the investigator in cases where the
             age, career, lifestyle, or sexual orientation of the patient ensured compliance.
             Reliable contraception had to be maintained throughout the study and for 7 days after
             study drug discontinuation. Periodic abstinence (eg, calendar, ovulation,
             symptothermal, post-ovulation methods) and withdrawal were not acceptable methods of
             contraception. Hormonal contraceptive use was disallowed.

          -  History of heart failure Grade II-IV according to the New York Heart Association
             (NYHA) classification.

          -  Second or third degree heart block with or without a pacemaker.

          -  Concomitant potentially life threatening arrhythmia or symptomatic arrhythmia.

          -  Angina pectoris of any type, including unstable angina pectoris.

          -  Clinically significant valvular heart disease.

          -  Evidence of a secondary form of hypertension, including but not limited to any of the
             following: coarctation of the aorta, hyperaldosteronism, unilateral or bilateral renal
             artery stenosis, Cushing disease, pheochromocytoma, polycystic kidney disease.

          -  Known moderate or malignant retinopathy, defined as: moderate (retinal signs of
             hemorrhage, microaneurysm, cotton-wool spot, hard exudates, or a combination thereof)
             or malignancy (signs of moderate retinopathy plus swelling of the optic disk).

          -  Evidence of hepatic disease as determined by any one of the following: aspartate
             aminotransferase (AST) or alanine aminotransferase (ALT) values greater than two times
             the upper limit of normal at Visit 1, a history of hepatic encephalopathy, a history
             of esophageal varices, or a history of a portocaval shunt.

          -  Evidence of renal impairment as determined by anyone of the following: serum
             creatinine > 1.5 times the upper limit of normal at Visit 1, a history of dialysis, or
             a history of nephrotic syndrome.

          -  History of clinically significant allergies including asthma, and/or multiple drug
             allergies.

          -  Any surgical or medical condition with the potential to significantly alter the
             absorption, distribution, metabolism, or excretion of any drug including but not
             limited to any of the following: history of major gastrointestinal tract surgery such
             as gastrectomy, gastroenterostomy, bowel resection, gastric bypass, gastric stapling,
             or gastric banding, currently active or active inflammatory bowel syndrome within 12
             months prior to Visit 1, currently active gastritis, ulcers, or
             gastrointestinal/rectal bleeding, or urinary tract obstruction regarded as clinically
             meaningful by the investigator.

          -  Any surgical or medical condition, which in the opinion of the investigator or the
             Novartis monitor, placed the patient at higher risk from his/her participation in the
             study, or were likely to prevent the patient from complying with the requirement of
             the study or completing the trial period.

          -  Volume depletion based on the investigator's clinical judgment using vital signs, skin
             turgor, moistness of mucous membranes, and laboratory values.

          -  Any chronic inflammatory condition requiring chronic anti-inflammatory therapy.

          -  History of malignancy of any organ system, treated or untreated, within the past 5
             years whether or not there was evidence of local recurrence or metastases, with the
             exception of localized basal cell carcinoma of the skin.

          -  History of drug of alcohol abuse within the last 2 years.

          -  Use of other investigational drugs at the time of enrollment, or within 30 days or 5
             half-lives of enrollment, whichever was longer.

          -  Inability to communicate and comply with all study requirements including the
             unwillingness or inability to provide informed consent.

          -  Persons directly involved in the execution of this protocol.

          -  History of non-compliance to medical regimens, or unwillingness to comply with the
             study protocol.

          -  Currently taking prohibited concomitant medications(s) listed and
             inability/unwillingness to discontinue them for the entire study period.

          -  Any severe, life-threatening disease within the past five years.

          -  Arm circumference > 42 cm for patients participating in ambulatory blood pressure
             monitoring (ABPM).