Lovastatin

Sponsored by: Kos Pharmaceuticals

Purpose: You are being asked to participate in a research study that will determine if Niacin ER/Lovastatin at two different doses compared to diet control (this group will receive a tablet containing 50 mg of immediate-release niacin) is a safe medicine that will reduce leg pain in subjects with intermittent claudication Niacin ER/Lovastatin is a combination of two FDA (United States Food and Drug Administration) approved cholesterol modifying medications: Niaspan[R] (extended-release niacin) and lovastatin, a stalin (the same medicine found in Mevacor[R]) Niacin ER/Lovastatin was approved by the FDA under the name of Advicor[TM] for use in the treatment of elevated cholesterol The use of Niacin ER/Lovastatin in the treatment of peripheral arterial disease and symptomatic relief of intermittent claudication is considered investigational. An investigational use is one that is not approved by the FDA.

At least 375 subjects, with a similar medical condition to yours will participate in this study This study will use competitive enrollment. This means that when a target number of subjects have entered the treatment phase of the study, all further enrollment will be closed. Therefore, it is possible that you could be in the screening phase, and be discontinued without your consent if the target number of subjects have already entered the study.

The purpose of this study is to evaluate the effect of Niacin ER/Lovastatin (at two different doses) compared with a diet-only control group in subjects with intermittent claudication (leg pain), a condition caused by narrowing of the leg arteries.

You will be monitored for up to six (6) weeks in order to determine if you qualify for the study During the six-week qualification period, you will return to the study center for 3-4 study visits Qualification for the study includes:

* having experienced "intermittent claudication" (leg pain) for at least 6 months

* 3-4 treadmill tests (walking tests)

* determination of your legs' blood pressure

If you qualify and choose to participate, your participation in this study will last approximately nineteen months.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Dose Comparison, Parallel Assignment, Safety/Efficacy Study

Ages eligible for study: 40 years and above, both genders

Inclusion Criteria:

1. Women must not be pregnant nor breast-feeding and not planning to become pregnant or to breast-feed. Women of childbearing potential must commit to using oral contraception, intrauterine device (IUD), or a double-barrier method of contraception. Women using oral contraception must have done so for 3 months prior to randomization, and continue to do so for the duration of the study. To be considered not of childbearing potential, women must be post-menopausal for at least 2 years or surgically sterile

2. Patient is willing to participate for the duration of the study and has provided written informed consent

3. Patient with a history of 1C 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

4. At screening, patient has a Peak Walking Time (PWT) of 1 to 20 minutes inclusive. For patients who do not require drug washout as listed in the Drug list 1 in Section 8.0, the PWT must be 1 to 15 minutes inclusive

5. At qualification, patient has a reproducible PWT variability of [less than or equal to] 20% between Qualification Visits 1 and 2 over a 4 to 10 day period1; if variability is > 20%, a third treadmill test will be performed (optional Qualification Visit 3) within an additional 4 to 10 days. In this case, there must be a variability of 20% [pounds sterling] between Qualification Visits 2 and 3 for patient qualification

AND

Patient has a mean PWT of 1 to 15 minutes inclusive calculated using the values of two consecutive visits (either for Qualification Visits 1 and 2, or for Qualification Visits 2 and 3).

6. Patient has a Doppler-measured pre-treadmill ABI of 0.90 or lower after 10 minutes of rest at Screening.

OR

If pre-treadmill ABI is > 0.90, a 20% reduction from the pre-treadmill ABI value, when measured within one minute after claudication-limiting treadmill testing, must be obtained. This will be evaluated at Screening only.

OR

For patients with an ABI of > 1.3 (non-compressible arteries), a first toe pressure measurement will be allowed. In this case, a Toe-Brachial Index (TBI) of < 0.7 must be obtained for patient qualification. TBI will be evaluated for screening purposes only.

7. Patient's baseline LDL-C level must be a mean value of < 160 mg/dL measured in Qualification Visits 1 and 2; if mean value is [greater than or equal to] 160 mg/dL, a third value (optional Qualification Visit 3) will be obtained within 4-10 days. In this case, the mean LDL-C of the last two tests must be < 160 mg/dL for patient qualification.

8. Patient is able to comply with the protocol procedures and all follow-up visits.

Location and Contact Information

Craig F. Amburgey, MS, Kos Pharmaceuticals, 14875 NW 77th Avenue, Suite 100, Miami Lakes, FL 33014; (800) 722-4567

Expected Total Enrollment: 375

Study ID Numbers: MA-02-010403; ICPOP

Estimated Completion Date March 2006

NLM Identifier NCT00062556

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