MedStar Authors catalog › Details for: Cholesterol ester transfer protein inhibition by TA-8995 in patients with mild dyslipidaemia (TULIP): a randomised, double-blind, placebo-controlled phase 2 trial.
Cholesterol ester transfer protein inhibition by TA-8995 in patients with mild dyslipidaemia (TULIP): a randomised, double-blind, placebo-controlled phase 2 trial. Journal: Lancet (London, England). ISSN: 0140-6736. UI/PMID: 26047975. Subject(s): Adolescent | Adult | Aged | *Cholesterol Ester Transfer Proteins/ai [Antagonists & Inhibitors] | Cholesterol, HDL/bl [Blood] | Cholesterol, HDL/de [Drug Effects] | Cholesterol, LDL/bl [Blood] | Cholesterol, LDL/de [Drug Effects] | Denmark | Double-Blind Method | *Dyslipidemias/dt [Drug Therapy] | Female | *Fluorobenzenes/ad [Administration & Dosage] | *Heptanoic Acids/ad [Administration & Dosage] | Humans | *Hydroxymethylglutaryl-CoA Reductase Inhibitors/ad [Administration & Dosage] | Male | Middle Aged | Netherlands | *Pyrimidines/ad [Administration & Dosage] | *Pyrroles/ad [Administration & Dosage] | Quinolines/ad [Administration & Dosage] | *Quinolines/pd [Pharmacology] | *Sulfonamides/ad [Administration & Dosage] | Treatment Outcome | Young Adult Institution(s): MedStar Health Research Institute Activity type: Journal Article. Medline article type(s): Clinical Trial, Phase II | Journal Article | Multicenter Study | Randomized Controlled Trial | Research Support, Non-U.S. Gov't Online resources: Click here to access online Digital Object Identifier: http://dx.doi.org/10.1016/S0140-6736(15)60158-1 (Click here) Abbreviated citation: Lancet. 386(9992):452-60, 2015 Aug 1. Local Holdings: Available online from MWHC library: 1995 - present, Available in print through MWHC library: 1983 - 2007. Abstract: BACKGROUND: Dyslipidaemia remains a significant risk factor for cardiovascular disease and additional lipid-modifying treatments are warranted to further decrease the cardiovascular disease burden. We assessed the safety, tolerability and efficacy of a novel cholesterol esterase transfer protein (CETP) inhibitor TA-8995 in patients with mild dyslipidaemia. Abstract: METHODS: In this randomised, double-blind, placebo-controlled, parallel-group phase 2 trial, we recruited patients (aged 18-75 years) from 17 sites (hospitals and independent clinical research organisations) in the Netherlands and Denmark with fasting LDL cholesterol levels between 25 mmol/L and 45 mmol/L, HDL cholesterol levels between 08 and 18 mmol/L and triglyceride levels below 45 mmol/L after washout of lipid-lowering treatments. Patients were randomly allocated (1:1) by a computer-generated randomisation schedule to receive one of the following nine treatments: a once a day dose of 1 mg, 25 mg, 5 mg, or 10 mg TA-8995 or matching placebo; 10 mg TA-8995 plus 20 mg atorvastatin; 10 mg TA-8995 plus 10 mg rosuvastatin or 20 mg atorvastatin or 10 mg rosuvastatin alone. We overencapsulated statins to achieve masking. The primary outcome was percentage change in LDL cholesterol and HDL cholesterol from baseline at week 12, analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01970215. Abstract: FINDINGS: Between Aug 15, 2013, and Jan 10, 2014, 364 patients were enrolled. At week 12, LDL cholesterol levels were reduced by 274% in patients assigned to the 1 mg dose, 327% in patients given the 25 mg dose, 453% in those given the 5 mg dose, and 453% in those given the 10 mg dose (p<00001). LDL cholesterol levels were reduced by 682% in patients given 10 mg TA-8995 plus atorvastatin, and by 633% in patients given rosuvastatin plus 10 mg TA-8995 (p<00001). A daily dose of 1 mg TA-8995 increased HDL cholesterol levels by 758%, 25 mg by 1243%, 5 mg by 1571%, and 10 mg dose by 1790% (p<00001). In patients receiving 10 mg TA-8995 and 20 mg atorvastatin HDL cholesterol levels increased by 1521% and in patients receiving 10 mg TA-8995 and 10 mg rosuvastatin by 1575%. We recorded no serious adverse events or signs of liver or muscle toxic effects. Abstract: INTERPRETATION: TA-8995, a novel CETP inhibitor, is well tolerated and has beneficial effects on lipids and apolipoproteins in patients with mild dyslipidaemia. A cardiovascular disease outcome trial is needed to translate these effects into a reduction of cardiovascular disease events.
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