A Safety and Efficacy Study of DRL-17822, a Cholesteryl Ester Transfer Protein (CETP) Inhibitor, in Patients With Abnormal Cholesterol Levels
Condition: Type II Hyperlipidemia
MeSH terms: Hyperlipoproteinemia Type II; Hyperlipidemias; Hyperlipoproteinemias
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to determine if a new drug, DRL-17822, is safe and effective in
      elevating high density lipoprotein cholesterol (HDL-C) and reducing low density lipoprotein
      cholesterol (LDL-C) in people with abnormal cholesterol levels that may put them at risk for
      heart disease.
    

Detailed description: 
      Cardiovascular disease is a leading cause of death worldwide. Among cardiovascular disorders,
      coronary heart disease (CHD) caused by atherosclerosis is the most common cause of morbidity
      and mortality. Prevention, stabilization and regression of atherosclerotic plaques may have a
      major impact on reducing the risk of acute coronary events.

      LDL-C lowering agents, primarily the statins, are the current mainstay in the pharmacologic
      management of dyslipidemia. However even with stain use, residual CHD risk from dyslipidemia
      remains. Epidemiologic and observational studies have shown that HDL-C is also a strong
      independent predictor of CHD, suggesting that raising HDL-C levels might afford clinical
      benefit in the reduction of cardiovascular risk.

      Presently only niacin is approved by the FDA for HDL-C elevation and can raise HDL-C levels
      by 20-30%. However its use can be limited by a high incidence of flushing and, less commonly,
      by elevation of blood glucose and potential hepatic toxicity.

      Cholesteryl ester transfer protein (CETP) inhibitors are being explored for their ability to
      elevate HDL-C. A small molecule CETP inhibitor, torcetrapib, has been demonstrated to elevate
      HDL-C by 60-100%. However, a large clinical trial (ILLUMINATE) where it increased HDL-C by a
      mean of 72% compared to baseline was halted as it failed to show benefit. Post-hoc analysis
      of this study implicated an off-target increase in blood pressure as potentially
      counteracting any anti-atherosclerotic benefits. Post-hoc subgroup analysis showed that
      patients in the highest HDL-C quartile had a 57% reduction in the risk of cardiovascular
      events.

      Increased blood pressure appears to be specifically related to torcetrapib as two other small
      molecule CETP inhibitors, anacetrapib and dalcetrapib, have not shown this in clinical trials
      and have been well tolerated. DRL-17822 has also not shown elevation of blood pressure in
      either animals or in normal volunteers.

      This study will investigate the efficacy and tolerability of DRL-17822 as dyslipidemia
      monotherapy in patients with Type II hyperlipidemia.
    

Intervention name(s): DRL-17822 or placebo
Intervention type(s): Drug
Intervention description(s): DRL-17822 50, 150 or 300 mg or matching placebo once daily after breakfast
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Randomized; Double-Blind; Placebo Controlled; Parallel Arm; Type II Hyperlipidemia; Cholesteryl Ester Transferase Protein Inhibitor; CETP Inhibitor