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TULIP: CETP inhibitor well tolerated, effective for treatment of mild dyslipidemia
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A novel cholesteryl ester transfer protein, or CETP, inhibitor appears to be well tolerated and effective in improving lipid profiles in patients with mild dyslipidemia, according to recent findings.
In the double blind, parallel-group phase 2 TULIP trial, researchers evaluated 364 men and women recruited from 17 sites in the Netherlands and Denmark. Participants were aged 18 to 75 years and had fasting cholesterol concentrations between 2.5 mmol/L and 4.5 mmol/L, HDL levels between 0.8 mmol/L and 1.8 mmol/L, and triglyceride levels less than 4.5 mmol/L after a run-in phase of 4 to 6 weeks.
Patients were randomly assigned at a 1:1 ratio to one of nine treatment regimens: 1 mg, 2.5 mg, 5 mg or 10 mg CETP inhibitor TA-8995 (Dezima) or placebo alone; 10 mg TA-8995 plus 20 mg atorvastatin; 10 mg TA-8995 plus 10 mg rosuvastatin; 20 mg atorvastatin alone or 10 mg rosuvastatin alone.
Study visits took place at baseline and at 4, 8 and 12 weeks, with follow-up 2 and 8 weeks after completion of treatment. The primary efficacy outcomes were percent change to LDL and HDL cholesterol at 12 weeks. Secondary outcomes included fasting total cholesterol, triglycerides, apolipoproteins A-I, B and E, and lipoprotein (a).
At 12 weeks, LDL cholesterol was reduced by 27.4% among patients who received the 1-mg TA-8995 dose, 32.7% among those assigned the 2.5-mg dose, 45.3% in patients assigned the 5-mg dose and 45.3% among those who received the 10-mg dose (P < .0001). LDL cholesterol decreased by 68.2% among patients who received 10 mg TA-8995 plus atorvastatin, and by 63.3% in patients treated with 10 mg TA-8995 plus rosuvastatin (P < .0001).
The daily regimen of 1 mg TA-8995 increased HDL cholesterol concentrations by 75.8%, the 2.5-mg daily dose by 124.3%, the 5-mg dose by 157.1% and the 10-mg dose by 179% (P < .0001). Participants treated with 10 mg TA-8994 plus atorvastatin demonstrated a 152.1% increase in HDL, whereas those receiving 10 mg TA-8995 plus rosuvastatin exhibited an HDL increase of 157.5%.
The researchers observed no significant changes to triglycerides or total cholesterol related to TA-8995. Apolipoprotein B decreased significantly in all TA-8995 monotherapy groups, ranging from 20% to 33.7% (P < .0001). Apolipoprotein A-1 and E also increased significantly among patients who received TA-8995, in a dose-dependent fashion. Lipoprotein (a) decreased significantly across all groups treated with TA-8995, either as monotherapy or in combination with a statin.
The majority of adverse events (96%) were considered mild or moderate. Serious adverse events occurred in eight patients, but none of the events were considered related to treatment. The most frequently observed events in the TA-8995 monotherapy groups included headache and nasopharyngitis.
“These findings are important because they provide clinicians with the evidence that CETP inhibition with TA-8995 is an effective LDL cholesterol-lowering and HDL cholesterol-increasing treatment with the aim to prevent [CVD],” the researchers wrote. “The translation of the antiatherogenic potential of TA-8995 recorded in this study into a reduction of future [CV] events warrants formal testing in a [CV] outcome trial.” – by Jennifer Byrne
Disclosure: The study was funded by Dezima and undertaken by Xention. Please see the study for a list of all of the researchers’ financial disclosures.
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