Whitehouse Station, NJ - Patient enrollment in a study designed to test the efficacy of a novel compound—niacin and laropiprant—in patients with heterozygous familial hypercholesterolemia (FH) has been placed on hold, according to a press release issued by Merck & Co, the sponsor of the study [1].

The study, known as Assessment of Coronary Health Using an Intima-Media Thickness (IMT) Endpoint for Vascular Effects (ACHIEVE), is a two-year study in FH patients and is designed to determine whether raising HDL-cholesterol levels with niacin reduces atherosclerosis as measured by carotid IMT. The study is an investigation of a novel combination tablet, known as Cordaptive, formerly MK-0524A, that was designed to help patients tolerate the long-term use of the HDL-cholesterol-raising treatment. The combination tablet contains extended-release niacin and a specific blocker of prostaglandin D2 to prevent flushing.

ACHIEVE includes a similar patient population as the recently presented and published Effect of Combination Ezetimibe and High-Dose Simvastatin vs Simvastatin Alone on the Atherosclerotic Process in Patients with Heterozygous Familial Hypercholesterolemia (ENHANCE) trial, a study that also used carotid IMT measurements as the primary outcome. Dr John Kastelein (Academic Medical Center, Amsterdam, the Netherlands), who was the lead investigator of ENHANCE, is the chair of the ACHIEVE steering committee.

Speaking with heartwire, Merck spokesperson Ron Rogers said enrollment has been placed on hold because the steering committee wants to look at "many factors," among them "the evolving science of IMT." The steering committee plans to examine data from ENHANCE, the torcetrapib studies Rating Atherosclerotic Disease Change by Imaging with a New Cholesteryl-Ester-Transfer Protein Inhibitor (RADIANCE) 1 and 2, Atorvastatin vs Simvastatin on Atherosclerosis Progression (ASAP), and a study testing the efficacy and safety of the acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor pactimibe for reducing the progression of carotid artery disease, known as CAPTIVATE.

Specifically, said Rogers, the committee plans to look at the patient population being studied, including the baseline LDL-cholesterol levels and degree of atherosclerosis in the carotid arteries of the FH patients, a group that has been treated aggressively with statins in the past. The ultrasound technology will also be under scrutiny. Rogers said it would be unfair to characterize enrollment being placed on hold because of the null findings from ENHANCE; rather, it is being done in light of evidence from these five IMT trials.

Initiated in October 2006, ACHIEVE investigators have enrolled approximately one-third of the planned 900 patients. Rogers said all patients enrolled in ACHIEVE will be followed according to protocol, and study data will remain blinded. The Food and Drug Administration accepted a new drug application (NDA) for Cordaptive in August 2007.

A clinical trial testing whether extended-release niacin and laropiprant, the prostaglandin D2 inhibitor, prevents MI, stroke, or revascularization procedures in 20 000 patients with existing vascular disease is currently under way at the Clinical Trial Service Unit (CTSU) of Oxford University. That study, known as the Heart Protection Study 2 Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE), remains unaffected by the decision to suspend enrollment in ACHIEVE. Results are expected in about four years.