| Eligibility |
Inclusion Criteria:
1. Age 40-80 years.
2. Patients diagnosed with PAD and IC for at least 6 months before screening and disease
assessed as stage II per the Fontaine classification.
3. Patients on stable medical therapy for PAD and IC symptoms, which may include
lifestyle modification (e.g., smoking cessation), a community- or home-based exercise
rehabilitation program, anti-platelet medications, and individual risk factor
intervention (e.g., lipid-lowering therapy, antihypertensive therapy, glycemic
control) unless individually contraindicated, for at least 3 months prior to the
screening visit.
4. For patients with reproductive potential, a willingness to use methods of
contraception that will prevent the patients or their partners from becoming pregnant
during the study.
Exclusion Criteria:
1. Participation in any clinical investigation within 4 weeks prior to enrollment or use
of other investigational drugs at the time of enrollment, or within 5 half-lives at
the time of enrollment, or until the expected PD effect has returned to baseline,
whichever longer.
2. Patients who meet any of the following PAD related criteria:
1. Patients with high variability in the walking distance, defined as the change
=25% in MWD between two 6-MWT with a time interval of two to three weeks.
2. Patients unable to hold all narcotic pain relievers for 24 hours prior to the
performance of the walking test.
3. Patients with any condition other than PAD that limits walking ability (e.g.,
orthopaedic disease, respiratory disease, neurological disorders).
4. Known inflammatory disease of the arteries (other than atherosclerosis, e.g.,
thromboangiitis obliterans).
5. Clinical evidence of critical limb ischemia including new or non-healing ulcers
(felt secondary to critical limb ischemia), new or recent onset of resting pain
in the lower extremities particularly at night (felt secondary to critical limb
ischemia) and/or gangrene of the lower extremities (Fontaine stage III-IV).
6. Patients actively attending and participating in a supervised exercise
rehabilitation program (patients who have already completed such a program and
remain symptomatic may be included).
3. Any of the following concomitant cardiovascular or metabolic conditions or diseases:
1. Myocardial infarction or angina pectoris within 6 months of screening.
2. Stroke within 3 months of screening.
3. History of clinically significant ventricular arrhythmias, according to the
discretion of the investigator, within 6 months of screening.
4. Patients with electronic cardiac pacemaker.
5. Significant ECG abnormalities (e.g., WPW syndrome), according to the discretion
of the investigator, at screening.
6. History of sustained and clinically significant supraventricular arrhythmias
(e.g., paroxysmal atrial fibrillation/flutter) within 6 months of screening.
7. Chronic heart failure New York Heart Association Class III or IV.
8. Known presence of aortic aneurysm > 5 cm.
9. Uncontrolled diabetes as defined by a random fasting glucose level of 13 mmol/L
or 240 mg/dL or a HbA1c greater than 9% as measured at screening.
10. Uncontrolled or resistant hypertension, defined as BP>160/100 mm Hg after
standard anti-hypertension treatment.
4. History of unstable or severe hepatic or renal disease or another medically
significant illness
5. History of any of the following chronic conditions:
1. Malignancy of any organ system (other than localized basal or squamous cell
carcinoma of the skin), treated or untreated, within the past 5 years, regardless
of whether there is evidence of local recurrence or metastases.
2. History of immunodeficiency diseases, including a positive HIV (ELISA and Western
blot) test result, and severe uncontrolled ulcerative colitis or Crohn's disease.
3. History of any hypercoagulable or bleeding disorders.
4. History of significant and active drug or alcohol abuse that could interfere with
conduct of the trial within the 12 months prior to dosing. Note: investigator may
establish veracity of patient history with drug or alcohol testing as deemed
necessary.
6. Dementia or other mental disorders (e.g., continues to receive medication or
psychological intervention) that prevent patients from following a research protocol.
7. Major surgical procedure before screening or planned to occur during the planned time
frame of the study.
8. History of multiple and clinically significant recurring drug allergies.
9. Use of strong inhibitors or strong inducers of CYP3A4 within 14 days or 5 half-lives
(whichever longer); or grapefruit juice or grapefruit containing products within 7
days prior to first study treatment.
10. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
female after conception and until the termination of gestation, confirmed by a
positive HCG laboratory test.
11. Any medical condition (e.g., with a plan to receive vaccination within study duration)
that in the opinion of the investigator may place the patient at higher risk from
his/her participation in the study.
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