An open-label, multicenter study to evaluate the efficacy and tolerability of a 4 week therapy with the combination of valsartan 160 mg plus amlodipine 5 mg in hypertensive patients not adequately responding to a 4 week treatment with amlodipine 5 mg or felodipine 5 mg in monotherapy - ExPress - M

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-001484-39-DE
• Date of registration: 24/05/2006
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma GmbH
• Public title: An open-label, multicenter study to evaluate the efficacy and tolerability of a 4 week therapy with the combination of valsartan 160 mg plus amlodipine 5 mg in hypertensive patients not adequately responding to a 4 week treatment with amlodipine 5 mg or felodipine 5 mg in monotherapy - ExPress - M
• Scientific title: An open-label, multicenter study to evaluate the efficacy and tolerability of a 4 week therapy with the combination of valsartan 160 mg plus amlodipine 5 mg in hypertensive patients not adequately responding to a 4 week treatment with amlodipine 5 mg or felodipine 5 mg in monotherapy - ExPress - M
• Date of first enrolment: 26/07/2006
• Target sample size: 230
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-001484-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: sequential, non-responder If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Germany

Key inclusion & exclusion criteria

Inclusion criteria:
- Male or female patients >= 18 years
- Patients with essential hypertension:
At Visit 1, untreated patients must have a MSSBP >= 160 mmHg and < 180 mmHg and treated patients need to have a MSSBP < 180 mmHg. Untreated patients can be included as soon as the safety laboratory parameters are available, but not at the day of Visit 1. This inclusion visit will be recorded as Visit 3 in the CRF.
At Visit 2, patients previously treated for hypertension need to have a MSSBP >= 160 mmHg and < 180 mmHg for entrance into the first treatment phase. Patients previously treated for hypertension who have a MSSBP < 160 mmHg at Visit 2 will continue the wash-out phase and will be again evaluated with regard to BP criteria at Visit 3. Untreated patients do not perform Visit 2.
At Visit 3, which is not performed for patients who entered the first treatment phase already at Visit 2, patients need to have a MSSBP >= 160 mmHg and < 180 mmHg for entrance into the first treatment phase.
At Visit 4, all patients need to have a MSSBP >= 140 mmHg for entrance into the second treatment phase
- Written informed consent to participate in the study prior to any study procedures

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- Patients with controlled blood pressure levels (MSSBP < 140 mmHg and MSDBP < 90 mmHg) under current antihypertensive therapy at Visit 1.
- MSDBP >= 110 mmHg or MSSBP >= 180 mmHg at any time between visit 1 and baseline
- Inability to completely discontinue all antihypertensive medications safely for a period of up to 2 weeks, as required by the protocol
- Known Keith-Wagener grade III or IV hypertensive retinopathy
- Evidence of a secondary form of hypertension, such as coarctation of the aorta, hyperaldosteronism, unilateral renal artery stenosis or pheochromocytoma
- History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures, known or suspected contraindications to angiotensin II receptor blockers or to CCBs as described in the SmPC (particularly amlodipine 5, felodipine 5, valsartan 160 mg)
- Heart failure NYHA II-IV
- Second or third degree heart block without pacemaker
- Concomitant unstable angina pectoris
- Concomitant potentially life-threatening arrhythmia or symptomatic arrhythmia
- Clinically significant valvular heart disease
- Transient ischemic cerebral attack, stroke, hypertensive encephalopathy or myocardial infarction prior to Visit 1
- Type 1 diabetes mellitus
- Type 2 diabetes mellitus with poor glucose control as defined by persistent fasting blood glucose > 11 mmol/l or > 200 mg/dl at Visit 1.
- Any surgical or medical condition which might 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, or bowel resection
Currently active, or active inflammatory bowel syndrome within 12 months prior to Visit 1
Currently active gastritis, ulcers or gastrointestinal/ rectal bleeding (hemorrhoids not included)
Any history of pancreatic injury, pancreatitis or evidence of impaired pancreatic function/ injury
Evidence of hepatic disease or cholestasis as determined by any one of the following: ALT or AST values > 2 x ULN at Visit 1, a history of hepatic encephalopathy, a history of esophageal varices, or a history of a portocaval shunt, obstruction of the biliary tract
Evidence of renal impairment as determined by any one of the following: serum creatinine > 1.5 x ULN at Visit 1, a history of dialysis, or a history of nephrotic syndrome
Current obstruction of the urinary tract or difficulty in voiding due to mechanical as well as inflammatory conditions which is likely to require intervention during the course of the study or is regarded as clinically meaningful by the investigator
- History of any severe, life-threatening disease
- History of drug or alcohol abuse within the last 2 years
- History of non-compliance to medical regimens, or those patients unwilling to comply with the trial protocol.
- Unwillingness or inability to give informed consent
- Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer
- History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ml)
- Women

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

moderate essential hypertension
MedDRA version: M15 Level: LLT Classification code 10015488

Intervention(s)

Trade Name: Diovan 160mg Filmtabletten
Product Name: Diovan 160 mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Valsartan
Current Sponsor code: VAL489
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 160-

Trade Name: Norvasc 5mg
Product Name: Norvasc 5mg
Pharmaceutical Form: Tablet
INN or Proposed INN: Amlodipine
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Trade Name: Felodipin Sandoz
Product Name: Felodipin Sandoz
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: Felodipine
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

Main Objective: To demonstrate that 4 weeks of treatment with valsartan 160 mg plus amlodipine 5 mg in combination provide an additional mean sitting systolic blood pressure reduction in patients not adequately responding (i.e., MSSBP = 140 mmHg) to 4 weeks of treatment with amlodipine 5 mg or felodipine 5 mg.

Secondary Objective: • To evaluate the effects of valsartan 160 mg and amlodipine 5 mg on mean sitting diastolic blood pressure, pulse pressure, heart rate, normalization and responder rate.
• To assess the safety and tolerability of valsartan 160 mg and amlodipine 5 mg.

Primary end point(s): The primary efficacy parameter of this trial is the change in trough MSSBP between Visit 4 (amlodipine 5 mg or felodipine 5 mg) and Visit 5 (valsartan 160 mg plus amlodipine 5 mg).

Secondary ID(s)

CVAA489ADE03