Official Title: “The Dose Response of Niacin ER/Lovastatin on Peak Walking Time (PWT) in Patients With Intermittent Claudication - a Matrix Design”

The purpose of this study is to compare the dose response and safety of Niacin ER/Lovastatin, Niaspan® and Lovastatin with each other, in subjects with leg pain caused by a narrowing of their leg arteries.

At least 870 subjects, with leg pain caused by a narrowing of their leg arteries will take part in this study.

Both Niaspan and lovastatin (Mevacor®) are approved by the United States Food and Drug Administration (FDA) to treat high cholesterol. Niacin ER/Lovastatin (Advicor®), a combination of these two drugs, is also approved by the FDA to treat high cholesterol. The use of Niacin ER/Lovastatin to treat narrowing of leg arteries and relieve “intermittent claudication” (leg pain caused by narrowing of the arteries in the leg) is considered investigational. An investigational use is one that is not approved by the FDA.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

This is a Phase 3, 32-week, double-blind, diet-intervention, randomized, parallel group, ten-arm, multi-center, multi-national, dose titration study evaluating the safety and efficacy of NL in patients with intermittent claudication (IC).

The objectives of this study are to evaluate the safety and efficacy of NL in patients with IC. The primary efficacy analysis will be the percent change from baseline in Peak Walking Time (PWT) calculated from the natural logarithm of the ratio of the time walked on treadmill at the Week 32 Visit divided by the time walked at baseline. Other efficacy measures will include Claudication Onset Time (COT) percent changes from baseline to Week 32 , changes in Ankle Brachial Index (ABI), Quality of Life (QoL) percent changes at Weeks 20 and 32, lower limb amputations, composite of cardiovascular events (MI, stroke, and vascular death), and coronary and peripheral artery revascularizations. Safety variables will include serum transaminases, routine chemistry parameters, hematology, and adverse events.

Pharmacokinetic analyses will be conducted as well.

Intervention(s) in this Clinical Trial

• Drug: Niacin Extended Release and Lovastatin Tablets

INCLUSION CRITERIA:

• Men & women at least 40 years of age or older. Women must not be pregnant nor breast-feeding & not planning to become pregnant or to breast-feed.
• History of IC of the lower extremities which has been present for at least 6 months with no change in symptoms in the previous 3 months prior to screening.
• LDL-C of <160 mg/dL and Triglycerides <800.

EXCLUSION CRITERIA:

• Severe neuropathy.
• Gross obesity (BMI ≥ 40).
• Presence of critical limb ischemia defined as ischemic rest pain, gangrene, ulceration, or pending amputation of a lower extremity due to severe PAD.
• Surgical intervention to alleviate symptoms of claudication within 6 months or endovascular interventions within 3 months.
• Documented CAD taking any cholesterol-modifying agent and unable to undergo washout as judged by the Investigator or due to personal choice.
• Systolic blood pressure ≥160 mmHg &/or diastolic blood pressure ≥95 mmHg.
• Presence of clinically significant laboratory test abnormalities for liver or renal function tests, thyroid function or HgbA1C.
• History of alcohol abuse or currently drinks alcohol in excess.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 40 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Kos Pharmaceuticals

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00071266

Study ID Number: MA-03-010401

ClinicalTrials.gov Identifier: NCT00071266

Health Authority: United States: Food and Drug Administration