SPIRIT III Clinical Trial of the XIENCE V® Everolimus Eluting Coronary Stent System (EECSS)

SPIRIT III: A Clinical Evaluation of the Investigational Device XIENCE V® Everolimus Eluting Coronary Stent System (EECSS) in the Treatment of Subjects With de Novo Native Coronary Artery Lesions

This study is divided into 5 arms:

1. Randomized Clinical Trial (RCT): Prospective, randomized, active-controlled, single blind, parallel two-arm multi-center clinical trial in the United States (US) comparing XIENCE V® Everolimus Eluting Coronary Stent System (CSS) (2.5, 3.0, 3.5 mm diameter stents) to the Food and Drug Administration (FDA) approved commercially available active control TAXUS® EXPRESS2™ Paclitaxel Eluting Coronary Stent (TAXUS® EXPRESS2™ PECS) System
2. US 2.25 mm non-randomized arm using 2.25 mm diameter XIENCE V® Everolimus Eluting CSS
3. US 4.0 mm non-randomized arm using 4.0 mm diameter XIENCE V® Everolimus Eluting CSS
4. US 38 mm non-randomized arm using 38 mm in length XIENCE V® Everolimus Eluting CSS
5. Japanese non-randomized arm using XIENCE V® Everolimus Eluting CSS (2.5, 3.0, 3.5, 4.0 mm diameter stents) in Japan

The TAXUS® EXPRESS2™ Paclitaxel Eluting Coronary Stent System is Manufactured by Boston Scientific.

The purpose of the SPIRIT III clinical trial is to evaluate the safety and efficacy of the XIENCE V® Everolimus Eluting Coronary Stent System (XIENCE V® EECSS). The XIENCE V® EECS (XIENCE V® arm) will be compared to an active control group represented by the FDA approved commercially available Boston Scientific TAXUS® EXPRESS2™ Paclitaxel-Eluting Coronary Stent (TAXUS® EXPRESS2™ PECS) System (TAXUS® arm).

The SPIRIT III clinical trial consists of a randomized clinical trial (RCT) in the US which will enroll approximately 1,002 subjects (2:1 randomization XIENCE V® EECS : TAXUS® EXPRESS2™ PECS) with a maximum of two de novo native coronary artery lesion treatment within vessel sizes >= 2.5 mm and <= 3.75 mm.

The SPIRIT III clinical trial also consists of three concurrent US non-randomized arms (2.25 mm diameter stent, 4.0 mm diameter stent and 38 mm length stent arms) and one Japanese non-randomized arm as follows:

1. 105 subjects with a maximum of two de novo native coronary artery lesion within vessel sizes > 2.25 mm and < 2.5 mm and lesion length <= 22 mm will be enrolled concurrently in the US 2.25 mm non-randomized treatment arm
2. 80 subjects with a maximum of two de novo native coronary artery lesion within vessel sizes > 3.75 mm and >= 4.25 mm and lesion length <= 28 mm will be enrolled concurrently in the US 4.0 mm non-randomized treatment arm
3. 105 subjects with a maximum of two de novo native coronary artery lesion within vessel sizes > 3.0 mm and < 4.25 mm and lesion length > 24 mm and < 32 mm will be enrolled concurrently in the US 38 mm non-randomized treatment arm.
4. 88 Japanese subjects with a maximum of two de novo native coronary artery lesions within vessel sizes >= 2.5 mm and <= 4.25 mm and lesion length <= 28 mm will be enrolled concurrently in the non-randomized Japanese arm.

All subjects in the RCT and the four non-randomized arms will be screened per the protocol required inclusion/exclusion criteria. The data collected will be compared to data from the subjects enrolled into the TAXUS® arm of US RCT.

Subjects enrolled in the US RCT will be sub-grouped based on whether they will have an angiographic and/or an intravascular ultrasound (IVUS) follow-up at 240 days as follows:

Group A: Angiographic and IVUS follow-up at 240 days (N=240) Group B: Angiographic follow-up at 240 days (N=324) Group C: No angiographic or IVUS follow-up (N=438)

All subjects will have clinical follow-up at 30, 180, 240 and 270 days (Data collected through 270 days will be submitted as the primary data set for US and Japanese market approval), and 1, 2, 3, 4, and 5 years (for annual reports).

All subjects enrolled into three US non-randomized arms (N=105 for 2.25 mm arm, N=80 for 4.0 mm arm and N=105 for 38 mm stent arm) will have clinical follow-up at 30, 180, 240, and 270 days, and angiographic follow-up at 240 days. No IVUS follow-up is required for subjects enrolled in these arms.

All subjects enrolled into the Japanese non-randomized arm (N=88) will have clinical follow-up at 30, 180, 240, and 270 days, and angiographic and IVUS follow-up at 240 days.

All subjects who receive a bailout stent will be assigned to Group A follow-up subgroup (angiographic and IVUS follow-up at 240 days after the index procedure), regardless of their primary assignment at randomization. At sites without IVUS capability, subjects receiving bailout stent will be assigned to Group B follow-up subgroup (angiographic follow-up at 240 days after the index procedure). Angiographic follow-up is required for all bailout subjects at 240 days.

Data from the US RCT will be submitted to the FDA as the primary data set for product approval for RVD >= 2.5 mm and <= 3.75 mm (2.5 mm, 3.0 mm and 3.5 mm stents). Combined data of the US trial/Japanese non-randomized arm will be submitted to the Japanese Ministry of Health, Labor and Welfare (MHLW) for Japanese approval for RVD>=2.5 mm and <= 4.25 mm (2.5 mm, 3.0 mm 3.5 mm and 4.0 mm stents). Data from the Japanese non-randomized arm will be submitted to the FDA as additional safety data. Data from the US non-randomized arms of the trial will be the primary data sets for approval for 2.25 mm diameter stent (RVD > 2.25 mm and < 2.5 mm), 4.0 mm diameter stent (RVD > 3.75 mm and <= 4.25 mm) and 38 mm length stent (RVD > 3.0 mm and <= 4.25 mm and lesion length > 24 mm and <= 32 mm), respectively in the US.

A pharmacokinetic substudy will be carried out in a minimum of 5 pre-determined sites in the US and a minimum of 5 pre-determined sites in Japan. In the US, the pharmacokinetics (PK) of everolimus, as delivered by the XIENCE V® EECS will be analyzed in a subset of 15 subjects (minimum) with single vessel/lesion treatment, and up to 20 subjects with dual vessel/lesion treatment, respectively. In Japan, a minimum of 10 subjects with single vessel/lesion treatment and up to 20 subjects with dual vessel/lesion treatment will have a PK measurements performed. These subsets will include subjects receiving overlapping stents.

Inclusion Criteria:

• Target lesion(s) must be located in a native epicardial vessel with visually estimated diameter between >= 2.25 mm and <= 4.25 mm and a lesion length <= 32 mm
• The target lesion(s) must be in a major artery or branch with a visually estimated stenosis of >= 50% and < 100% with a thrombolysis in myocardial infarction (TIMI) flow of >= 1
• Non-study, percutaneous intervention for lesions in a non-target vessel is allowed if done >= 90 days prior to the index procedure (subjects who received brachytherapy will be excluded from the trial)

Exclusion Criteria:

• Located within an arterial or saphenous vein graft or distal to a diseased (vessel irregularity per angiogram and > 20% stenosed lesion by visual estimation) arterial or saphenous vein graft
• Lesion involving a bifurcation >= 2 mm in diameter or ostial lesion > 50% stenosed by visual estimation or side branch requiring predilatation
• Located in a major epicardial vessel that has been previously treated with brachytherapy
• Located in a major epicardial vessel that has been previously treated with percutaneous intervention < 9 months prior to index procedure
• Total occlusion (TIMI flow 0), prior to wire passing
• The target vessel contains thrombus
• Another significant lesion (> 40% diameter stenosis [DS]) is located in the same epicardial vessel as the target lesion