An open-label, multicenter study to evaluate the efficacy and tolerability of a 4 week therapy with the fixed dose combination of amlodipine 10 mg plus valsartan 160 mg in hypertensive patients not adequately responding to a 4 week therapy with the free combination of an angiotensin receptor blocker (olmesartan 20 mg) plus amlodipine 10 mg - EXPRESS-O

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-001374-87-DE
• Date of registration: 11/05/2007
• 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 fixed dose combination of amlodipine 10 mg plus valsartan 160 mg in hypertensive patients not adequately responding to a 4 week therapy with the free combination of an angiotensin receptor blocker (olmesartan 20 mg) plus amlodipine 10 mg - EXPRESS-O
• Scientific title: An open-label, multicenter study to evaluate the efficacy and tolerability of a 4 week therapy with the fixed dose combination of amlodipine 10 mg plus valsartan 160 mg in hypertensive patients not adequately responding to a 4 week therapy with the free combination of an angiotensin receptor blocker (olmesartan 20 mg) plus amlodipine 10 mg - EXPRESS-O
• Date of first enrolment: 17/07/2007
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-001374-87
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Germany

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female patients ? 18 years
2. Patients with essential hypertension:
- At Visit 1, untreated patients must have an MSDBP ? 100 mmHg and < 110 mmHg and treated patients need to have an MSDBP < 110 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 an MSDBP ? 100 mmHg and < 110 mmHg for entry into the first treatment phase. Patients previously treated for hypertension who have an MSDBP < 100 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 an MSDBP ? 100 mmHg and < 110 mmHg for entry into the first treatment phase.
- At Visit 4, all patients need to have an MSDBP ? 90 mmHg for entry into the second treatment phase
3. 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:
1. Patients with controlled blood pressure levels (MSSBP < 140 mmHg and MSDBP < 90 mmHg) under current antihypertensive therapy at Visit 1.
2. MSDBP ? 110 mmHg or MSSBP ? 180 mmHg at any time between visit 1 and baseline
3. Inability to completely discontinue all antihypertensive medications safely for a period of up to 2 weeks, as required by the protocol
4. Known Keith-Wagener grade III or IV hypertensive retinopathy
5. Evidence of a secondary form of hypertension, such as coarctation of the aorta, hyperaldosteronism, unilateral renal artery stenosis or pheochromocytoma
6. 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 diuretics as described in the SmPC (particularly olmesartan 10-20 mg, amlodipine 5-10 mg, amlodipine 10mg/valsartan 160 mg)
7. Heart failure NYHA II-IV
8. Second or third degree heart block without pacemaker
9. Concomitant refractory angina pectoris
10. Concomitant potentially life-threatening arrhythmia or symptomatic arrhythmia
11. Clinically significant valvular heart disease
12. Transient ischemic cerebral attack, stroke, hypertensive encephalopathy or myocardial infarction prior to Visit 1
13. Type 1 diabetes mellitus
14. 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.
15. 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 or active acute glomerulonephritis 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
16. Therapy resistant hypokalemia, hypercalcemia, symptomatic hyperuricemia or sodium depletion (< 134 mmol/l), patients with volume depletion.
17. History of any severe, life-threatening disease
18. History of drug or alcohol abuse within the last 2 years
19. History of non-compliance to medical regimens, or those patients unwilling to comply with the trial protocol.
20. Any condition, which in the judgment of the investigator or medical monitor, would jeopardize the evaluation of efficacy or safety
21. Any surgical or medical conditions which, at the discretion of the investigator, place the patient at higher risk from his/her participation in the study, or are likely to prevent the patient from complying with the requirements of th

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

Health Condition(s) or Problem(s) studied

essential hypertension
MedDRA version: 9.1 Level: LLT Classification code 10020772 Term: Hypertension

Intervention(s)

Trade Name: Exforge 10 mg/160 mg Filmtabletten
Product Name: Exforge 10mg/160mg Filmtabletten
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Amlodipine
CAS Number: 111470-99-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
INN or Proposed INN: Valsartan
CAS Number: 137862-53-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 160-

Trade Name: Norvasc 5 mg
Product Name: Norvasc 5 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: Amlodipin
CAS Number: 111470-99-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Trade Name: HCT Sandoz 12,5 mg
Product Name: HCT Sandoz 12,5 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: Hydrochlorothiazide
CAS Number: 58-93-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 12.5-

Trade Name: Olmetec 10 mg Filmtabletten
Product Name: Olmetec 10 mg Filmtabletten
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Olmesartan medoximil
CAS Number: 144689-24-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Primary end point(s): The aim of this multicenter open-label trial is to evaluate the reduction in trough MSDBP by a 4-week treatment with the fixed dose combination of amlodipine 10 mg and valsartan 160 mg in hypertensive patients not adequately controlled by olmesartan 20 mg in free combination with amlodipine 10 mg. The main interest is the estimation and testing of the changes in BP between Visit 4 and Visit 5.

Secondary Objective: To evaluate the effects of 4 weeks of treatment with amlodipine 10 mg / valsartan 160 mg in fixed dose combination in patients not adequately responding (i.e., MSDBP = 90 mmHg) to 4 weeks of treatment with an angiotensin receptor blocker plus amlodipine 10 mg in free combination (olmesartan 20 mg plus amlodipine 10 mg) on mean sitting systolic blood pressure, pulse pressure, heart rate, normalization and responder rate.
To assess the safety and tolerability of amlodipine 10 mg / valsartan 160 mg.

Main Objective: To demonstrate that 4 weeks of treatment with amlodipine 10 mg plus valsartan 160 mg in fixed dose combination provide an additional mean sitting diastolic blood pressure reduction in patients not adequately responding (i.e., MSDBP = 90 mmHg) to 4 weeks of treatment with an angiotensin receptor blocker plus amlodipine 10 mg in free combination (olmesartan 20 mg plus amlodipine 10 mg).

Secondary ID(s)

CVAA489ADE06