A 12 week treatment, open-label, multicenter study to investigate the efficacy and safety of valsartan 160-320 mg with regard to effects on lipid subfractions in hypertensive patients with metabolic syndrome

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-003606-28-DE
• Date of registration: 02/11/2005
• Prospective Registration: No
• Primary sponsor: Novartis Pharma GmbH
• Public title: A 12 week treatment, open-label, multicenter study to investigate the efficacy and safety of valsartan 160-320 mg with regard to effects on lipid subfractions in hypertensive patients with metabolic syndrome
• Scientific title: A 12 week treatment, open-label, multicenter study to investigate the efficacy and safety of valsartan 160-320 mg with regard to effects on lipid subfractions in hypertensive patients with metabolic syndrome
• Date of first enrolment: 28/10/2005
• Target sample size: 75
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-003606-28
• 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: 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 outpatients = 18 years of age at Visit 1
2. MSSBP = 140 mmHg and < 170 and/or MSDBP = 90 mmHg and < 105 mmHg at Visit 2 for previously treated patients and at Visit 1 and 2 for previously untreated patients.
3. Fasting triglycerides greater than or equal to 150 mg/dL (1.69 mmol/L) at V1
4. Metabolic syndrome as defined by ATP III (involving one or more of the following) at Visit 1 (high triglycerides and elevated BP are mandatory in this trial):
• Central/abdominal obesity as measured by waist circumference (Men > 102 cm; Women > 88 cm)
• HDL cholesterol [Men < 40 mg/dL (1.04 mmol/L); Women < 50 mg/ dL (1.29 mmol/L)]
• Fasting glucose greater than or equal to 110 mg/dL (6.1 mmol/L)
5. Written informed consent to participate in this 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. MSSBP = 170 mmHg and/or MSDBP = 105 mmHg at any time between Visit 1 and Visit 2
2. Fasting plasma glucose = 126 mg/dl at Visit 1
3. Fasting LDL cholesterol = 160 mg/dl, fasting triglycerides = 600 mg/dl at Visit 1
4. Inability to discontinue all antihypertensive medications safely for a period of three weeks prior to initiation of treatment
5. Patients treated with lipid lowering drugs in the last 6 weeks prior to Visit 1, use of probucol in the last 6 months prior to V1
6. History of hypersensitivity to valsartan, inactive ingredients of valsartan capsules or to drugs with similar chemical structures
7. A history of cardiovascular disease, including angina pectoris, myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, transient ischemic attack, stroke, and peripheral artery disease
8. Known Keith-Wagener grade III or IV hypertensive retinopathy
9. Second or third degree heart block without a pacemaker, concurrent potentially life threatening arrhythmia or symptomatic arrhythmia, clinically significant valvular heart disease
10. Heart failure NYHA II -IV
11. Evidence of a secondary form of hypertension, to include coarctation of the aorta, hyperaldosteronism, Cushing’s disease, unilateral or bilateral renal artery stenosis, pheochromocytoma, polycystic kidney disease
12. Evidence of hypercholesterolemia secondary to other causes. This includes, but is not restricted to: alcoholism, auto-immune disease, nephrotic syndrome, any viral or non-viral hepatitis clinically active within 12 months prior to Visit 1, obstructive hepatic or biliary disease, dys- or macroglobulinemia, multiple myeloma, glycogen storage disease, uncontrolled hypothyroidism or hyperthyroidism, chronic pancreatitis and porphyria
13. Diabetes mellitus type I or II
14. Major depression requiring pharmacolgical treatment
15. Evidence of hepatic disease as determined by AST (SGOT) or ALT (SGPT) values > 3 x ULN at Visit 1
16. A history of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt
17. Evidence of renal impairment as determined by one of the followings: serum creatinine > 1.5 x ULN at Visit 1, a history of dialysis, or a history of nephrotic syndrome. If creatinine is found to be between 1.5 and 2 x UNL, a retest can be performed prior to initiation of treatment
18. Any severe, life-threatening disease within the past five years
19. 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, gastric bypass, gastric stapling, or gastric banding
- Currently active or active inflammatory bowel disease during the 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
20. Any surgical or medical condition which, at the discretion of the investigator, places 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 the study or completing the trial period
21. History of drug or alcohol abuse within the last 2 years
22. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 halflives before enrollment, whicheve

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

Health Condition(s) or Problem(s) studied

patients with hypertension and metabolic syndrome (ATP III)
MedDRA version: 4.0 Level: LLT Classification code 10052066

Intervention(s)

Product Name: Diovan 160 mg
Product Code: Valsartan
Pharmaceutical Form: Capsule*
INN or Proposed INN: Valsartan
CAS Number: 137862-53-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 160-

Primary Outcome(s)

Primary end point(s): The primary analysis will be the analysis of Apo B in LDL5+6 as reduction from baseline to study finalization.

Main Objective: To demonstrate that valsartan 320 mg has a positive effect on small, dense LDL subfractions (LDL 5+6) in hypertensive patients with metabolic syndrome after 12 weeks of treatment.

Secondary Objective: To evaluate whether valsartan 320 mg has positive effects on further lipid subfractions and enzymes related to the lipoprotein metabolism. These parameters are: derived mean LDL-density, derived mean LDL-size, concentrations of cholesterol in VLDL, IDL, LDL, LDL-subfractions (LDL-1 to LDL-6), HDL, HDL-subfractions (HDL 2b, HDL 2a, and HDL 3), and PAF-AH activity.
To evaluate the effect of valsartan 160-320 mg on blood pressure and pulse rate.
To assess the safety and tolerability of valsartan 160-320mg.

Secondary ID(s)

CVAL489ADE25