Local Delivery of Paclitaxel Via the TAPAS Catheter to Prevent Restenosis From Percutaneous Femoropopliteal Intervention

Peripheral artery disease (PAD) of the lower extremities is an extremely prevalent disorder
and is an important cause of morbidity that affects more than 10 million people in the
United States. This disorder is typically caused by atherosclerosis that limits blood flow
to the limbs, particularly due to stenosis or occlusion of the superficial femoral artery
(SFA) and/or popliteal artery. Although many patients are asymptomatic or are treated with
lifestyle changes, such as exercise therapy, or pharmacological treatment, including statins
and anti-platelet therapy, about 10-15% of patients have progressive symptoms which in
severe cases may lead to amputation.

Endovascular treatment with percutaneous vascular intervention (PVI), which includes
percutaneous transluminal angioplasty (PTA), stenting, atherectomy and thrombolytic therapy,
can provide excellent acute success rates greater than 90-95% However, the intermediate to
long-term patency rates of these arteries is hampered by neointimal hyperplasia resulting in
restenosis of the artery. This occurs with all endovascular therapy to some degree in both
the coronary and peripheral arena. With PVI in the superficial femoral and popliteal
arteries the restenosis rates are approximately 30-40% at 12 months, depending on the
complexity and severity of the disease.

In the coronary field, stents are now coated with anti-restenotic pharmacologic agents (drug
eluting stents—DES) such as paclitaxel and sirolimus-like drugs that prevent neointimal
growth. There have been published reports of significant efficacy in preventing restenosis
in the SFA by coating balloons with paclitaxel (drug eluting balloons—DEB) as well as a
nitinol stent. Despite the fact that these products are CE Mark approved and available in
Europe, currently there are no US FDA approved drug-eluting devices for use in PVI. Thus,
there remains a need for an alternative therapy to prevent restenosis in the SFA following
endovascular intervention.

Administration of intra-arterial paclitaxel mixed with iodinated contrast has been shown to
inhibit restenosis in a porcine coronary model.

Delivering paclitaxel intra-arterially in the coronary tree following stent implantation has
shown benefit in reducing the incidence of restenosis. The novel Targeted Adjustable
Pharmaceutical Application System (TAPAS)—TAPAS Catheter Therapeutic Infusion System
(ThermopeutiX, San Diego, CA, USA)—is a drug delivery catheter that consists of a proximal
and distal occlusion balloon with an adjustable length that allows a drug to dwell in a
specific segment of the artery for a period of time. The drug can then be aspirated and
discarded to avoid systemic exposure.

The PacTAP study is a randomized, double blind, placebo-control study to assess the safety
and efficacy of delivering intra-arterial paclitaxel via the TAPAS catheter following PVI to
prevent restenosis.

Inclusion Criteria:

- Age ≥ 18 years old.

- Subject able to provide informed consent and agree to all follow up requirements.

- Peripheral arterial disease with Rutherford Class 2-5.

- Successful percutaneous revascularization of the femoropopliteal artery (< 20%
residual stenosis by visual estimate) using standard techniques per discretion of the
local operator.

- The femoropopliteal Reference Vessel Diameter (RVD) must be ≥4.0 mm and ≤7.0 mm

Exclusion Criteria:

- Patient is pregnant or breast feeding. (Female subjects of childbearing potential
must have negative serum pregnancy test the day of the procedure.)

- Life expectancy < 12 months.

- Contraindication to aspirin, anti-platelet/anti-coagulant therapies required for
procedure/follow up.

- Known allergy to contrast media that cannot adequately be pre-medicated prior to
study procedure.

- Known allergy to paclitaxel.

- Uncontrolled hypercoagulability or history of HIT or HITTS syndrome.

- Simultaneous enrollment in another investigational device or drug study.

- Previous intervention of the target limb with a drug eluting stent or drug eluting
balloon.

- Absence of at least 1 TIMI-3 vessel run off into the foot.

- Total bilirubin > 2x upper limit of normal (ULN).

- ALT or AST > 3x ULN.

- Platelet count < 100,000/mm3.

- White blood cell count < 1.5/mm3.

- Any evidence of perforation or dye extravasation during the index procedure, even if
successfully treated with a covered stent.