RESTORE-IT-Study of Rifalazil in Chlamydia Pneumoniae Seropositive Patients With a History of Atherosclerotic Disease

• Male or female patients between 50 and 85 years of age.
• Patient has seropositive evidence of C. pneumoniae defined by IgG antibody titers ≥ 1:128 on microimmunofluorescence assay.

• The patient meets at least one of the following criteria:

  1. Diagnosis of PAD: i. Ankle-brachial index (ABI) of \<0.90 at rest in either leg, or toe brachial index of \< 0.7 if ankle pressure is calcified. ii. Known PAD on the basis of history or symptoms of intermittent claudication, prior endovascular or surgical revascularization.
  2. Known large vessel (non-cardioembolic) cerebrovascular event (stroke or TIA) within the last three years or carotid stenosis of >40% and ≤ 80% by Doppler ultrasound or asymptomatic carotid artery disease defined by a total plaque area >100 mm2and carotid stenosis of ≤ 80%by Doppler ultrasound.
  3. Known coronary artery disease on the basis of an exercise tolerance test positive for myocardial ischemia, or history of a prior myocardial infarction (greater than 6 months), or prior percutaneous coronary intervention and/or surgical revascularization (greater that 6 months).
• Patient has a maximal IMT measurement by ultrasound in either the left or right common carotid artery of ≥ 0.70 mm and at least one or more echogenic carotid plaques detectable in either the right or left side of the carotid artery.
• Patient is able to undergo magnetic resonance (MR) examination and MR baseline images obtained are of suitable image quality for analysis.
• If patient is taking cilostazol, pentoxifylline, or other approved drugs for the treatment of PAD and/or intermittent claudication or taking a statin, patient has to be on the medication for at least 6 months prior to Screening.
• Patients who have recently discontinued medications for PAD and/or intermittent claudication or statin must "wash-out" for at least one month prior to screening.
• Male and female patients must agree to use an effective form of birth control throughout the study period.

Exclusion Criteria:

• The patient lacks evidence of intermediate or advanced carotid atherosclerotic lesions or has heavily calcified plaque or poor image quality of their carotid arteries as determined by the MRI lab.
• Patient has critical limb ischemia as evidenced by ischemic rest pain, ulceration, or gangrene.
• Patient has new, previously unrecognized clinically significant electrocardiogram (ECG) abnormalities.
• Patient has liver function tests > 3.0 times the upper limit of normal, serum creatinine > 1.8 mg/dL for females and >2.0 mg/dL for males and a eGFR value \<30 mL/min/1.73 m2. Enrollment of patients with eGFR values of between 30 and 59 mL/min/1.73 m2 will be left to the discretion of the investigator. Patients with abnormal laboratory values which are deemed clinically significant by the investigator will not be enrolled.
• Patient has had a recent (\< 6 months) coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), carotid endarterectomy (CEA), carotid artery stent, or lower extremity revascularization/amputation.
• Patient plans for surgical/endovascular intervention for carotid and/or coronary during the course of the study.
• Patient has or being evaluated or treated for tuberculosis. Patients who were treated previously for tuberculosis but presently have inactive disease may be included.
• Patient has a chest x-ray obtained within the last month that is consistent with possible tuberculosis.
• Patient has a history of malignant neoplasm within the previous 5 years (except curable non-melanoma skin malignancies).
• Patient has a known immunodeficient state or is being treated with immunosuppressive drugs including high-dose steroids or cyclosporine.
• Patient has an active infection requiring systemic or oral antibiotics. Patients with prior infection must have discontinued such treatments at least 14 days prior to administration of investigational agent.
• Patient has an uncontrolled, unstable or recently diagnosed autoimmune disease, including but not limited to systemic lupus, inflammatory bowel disease, sarcoidosis, rheumatoid arthritis, or psoriasis.
• Patient has a recent history of alcohol abuse, illicit drug use or drug abuse or significant mental illness.
• Patient has a known or suspected allergy to the study medication(s) or class of study medication (rifamycins).
• Patient chronically uses antibacterials or has previously received rifalazil.
• Patient has a known or suspected allergy to MRI contrast agents (e.g., gadolinium) and/or has any medical or physical condition that would prevent them from receiving a gadolinium-based contrast agent or an MRI examination.
• Patient has participated in any clinical trial of an investigational drug, device, or medical procedure within 30 days prior to Baseline of the study.
• Patient is enrolled or plans to enroll in another clinical drug or device/interventional trial during this study.