Fixed-dose combination of rosuvastatin and valsartan for dual target achievement in patients with hypertension and hyperlipidaemia (UNIFY)

Phase 1

• Conditions: Patients with mild to moderate essential arterial hypertension AND primary hypercholesterolemia or mixed dyslipidaemia (LDL-c < 4.9 mmol/L or <189.5 mg/dl) with moderate, high or very high risk for cardiovascular event.; MedDRA version: 20.0 Level: PT Classification code 10062060 Term: Hyperlipidaemia System Organ Class: 10027433 - Metabolism and nutrition disorders; MedDRA version: 20.0 Level: PT Classification code 10015488 Term: Essential hypertension System Organ Class: 10047065 - Vascular disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2017-003672-31-HU
• Lead Sponsor: KRKA, d.d., Novo mesto

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-10-24
• Last Update Posted: 25 November 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 280

Inclusion Criteria

•Patients with mild to moderate essential AH* AND primary hypercholesterolemia or mixed dyslipidaemia (LDL-c < 4.9 mmol/L or <189.5 mg/dl) with moderate, high or very*** high risk for CV event.

•Female and male patients, aged 18-75 years
•Written informed consent
•Ability to adhere to trial protocol
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Additional explanation of inclusion criteria:
onaïve patients with newly diagnosed AH* and newly diagnosed primary hypercholesterolemia or mixed dyslipidaemia** with moderate, high or very high*** risk for CV event
oPatients with newly diagnosed primary hypercholesterolemia or mixed dyslipidaemia** and controlled or uncontrolled* AH

oPatients with newly diagnosed mild to moderate essential AH* and controlled or uncontrolled** primary hypercholesterolemia or mixed dyslipidaemia
oPatients with uncontrolled AH* and uncontrolled primary hypercholesterolemia or mixed dyslipidaemia**

*SBP 140-179 mmHg and AND DBP 90-109 mmHg
** type IIb (LDL-c < 4.9 mmol/L or < 189.5 mg/dl)
*** Among very high risk patients only patients with diabetes mellitus without target organ damage can be included.

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 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25

Exclusion Criteria

•Patients unsuccessfully treated with 2 or more different active substances at once for lowering blood pressure whenever in the past.
•Secondary AH (e.g. pheochromocytoma, primary aldosteronism, renal artery stenosis).
•Suspected resistant hypertension or grade 3 of hypertension (SBP=180 mmHg and/or DBP=110mmHg).
•LDL-c level equal or higher than 4.9 mmol/L (189,5 mg/dL)
•Diabetes with target organ damage (e. g. proteinuria).
•Previous CV event (e.g. MI, transient ischemic attack, stroke…).
•History of adverse reactions or hypersensitivity associated with the use of active substances, any other angiotensin II receptor blocker, any other statin or any components of the investigational medicinal products used in the trial.
•Concomitant treatment with:
- antihypertensive drugs used for other indication than AH (e.g. tachyarrhythmia, glaucoma) less than 3 months before the study or in changed dosages less than 3 months before the study
- drugs that may produce an increase in BP: systemic corticosteroids, hormonal medications (chronically used oral contraceptives are allowed), adrenergic receptor agonists, cyclosporine, erythropoietin, migraine medications such as triptans.
- other lipid-lowering drugs (besides those allowed in protocol): statins, fibrates, nicotinic acid, bile acid exchangers, probucol, ezetimibe.
- drugs that may increase the incidence of myositis, myopathy and rhabdomyolyisis if used with HMG-CoA reductase inhibitors (as rosuvastatin) fibric acid derivates including gemfibrozil, cyclosporine, nicotinic acid, azole antifungals, protease inhibitors and macrolide antibiotic, systemic formulation of fusidic acid or within 7 days of stopping fusidic acid treatment.
-drugs which increase systemic exposure to rosuvastatin: various protease inhibitors (for ex. atazanavir, lopinavir, tipranavir) in combination with ritonavir.
-lithium
-acetylsalicylic acid in a dose more than 3 g per day
-heparin
•Patients to whom ß-blocker therapy cannot be discountinued in one day.
•Renal dysfunction (creatinine clearance < 60 ml/min).Predisposition for development of renal failure (sepsis, hypotension, trauma, severe metabolic, endocrine and electrolyte disorders, uncontrolled seizures).
•Hepatic impairment (mild, moderate and severe), biliary cirrhosis and cholestasis, active liver disease including unexplained, persistent elevations of serum transaminases and any serum transaminase elevation exceeding 3 x the upper limit of normal (ULN).
•Pregnancy and lactation
•Personal or family history of hereditary muscular diseases and previous history of muscular toxicity with use of statins or fibrates, rabdomyolysis, myopathy.
•Elevated CK levels at baseline (>5xULN).
•Interstitial lung disease.
•History of angioedema (hereditary, idiopathic or related to previous treatment).
•Hypertensive encephalopathy.
•Normal average 24-hour SBP AND DBP obtained by 24h ABPM (<130/80 mmHg at baseline) (if patient’s 24h BP is over 130/80 mmHg, but patient’s office BP below 140/90 mmHg, patient is not included

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified