Peripheral Arterial Disease
Conditions
Brief summary
Efficacy and Safety of Combined Cilostazol and Rosuvastatin Therapy Versus Rosuvastatin Alone in Patients with Chronic Lower Extremity Peripheral Artery Disease: A Multicenter, Double-Blind, Randomized Controlled Trial
Interventions
DRUGUI022 or UI023 and co-administration of matching placebo
Run-in period: UIC201802 1 Tab/day + UIC201604 1 Tab/day, or UIC201803 1 Tab/day + UIC201801 1 Tab/day, for 4 weeks Treatment period: UI022 1 Tab/day + UIC201804 1 Tab/day, or UI023 1 Tab/day + UIC201805 1 Tab/day, for 24 weeks
DRUGUIC201604 or UIC201801 and co-administration of matching placebo
Run-in period: UIC201802 1 Tab/day + UIC201604 1 Tab/day, or UIC201803 1 Tab/day + UIC201801 1 Tab/day, for 4 weeks Treatment period: UIC201604 1 Tab/day + UIC201802 1 Tab/day, or UIC201801 1 Tab/day + UIC201803 1 Tab/day, for 24 weeks
Sponsors
Korea United Pharm. Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects must meet all of the following criteria. Screening Inclusion Criteria 1. Subjects aged 19 years or older. 2. Subjects with lower limb ischemic symptoms persisting for at least 24 weeks before screening. 3. Subjects who have been taking a statin according to dyslipidemia treatment guidelines for at least 12 weeks before screening. 4. Subjects with stable symptoms without significant improvement during the 12 weeks before screening, with a response of 3 or less to KPAQ Question 3 and a KPAQ summary score of 60 or less. 5. Subjects with ABI ≤ 0.9 at screening.Subjects with 0.9 \< ABI ≤ 1.0 may participate if arterial stenosis of 50% or more is confirmed by vascular imaging. 6. Subjects with Fontaine Stage II, including Stage IIa or IIb. 7. Subjects who voluntarily provide written informed consent to participate in the clinical trial. Randomization Inclusion Criteria 1. Subjects whose KPAQ summary score differs by no more than 10% between the screening visit and baseline visit. 2. Subjects who are able to maintain the dose of rosuvastatin, the run-in medication, during the treatment period. 3. Subjects with compliance of 70% or higher with the run-in medication during the run-in period
Exclusion criteria
Subjects who meet any of the following criteria are not eligible to participate in this clinical trial. 1. Subjects who underwent an endovascular procedure, surgery, or reconstruction within 24 weeks before the screening visit, or who are expected to require such a procedure, surgery, or reconstruction during the clinical trial. 2. Subjects with any of the following medical histories at the screening visit: 1\) Myocardial infarction, unstable angina, transient ischemic attack, stroke, coronary artery bypass graft, or coronary angioplasty within 12 weeks. 2\) Deep vein thrombosis within 12 weeks. However, subjects with isolated calf vein thrombosis may participate. 3\) Intolerance to statins, such as myopathy including rhabdomyolysis. 4) Malignant tumor within 5 years. 5) Alcohol or drug abuse. 3. Subjects with any of the following concomitant diseases at the screening visit: 1. Moderate or severe lower limb pain caused by spinal disease, such as spinal stenosis. 2. Congestive heart failure. 3. Bleeding, including hemophilia, capillary fragility, intracranial hemorrhage, upper gastrointestinal bleeding, urinary tract bleeding, hemoptysis, or vitreous hemorrhage, or a bleeding tendency, including active peptic ulcer, hemorrhagic stroke within 24 weeks before screening, surgery within 12 weeks before screening, or proliferative diabetic retinopathy. 4. Severe renal impairment, defined as Clcr \< 30 mL/min. 5. Uncontrolled diabetes mellitus, defined as HbA1c \> 9%. 6. Uncontrolled hypertension, defined as SBP \> 180 mmHg or DBP \> 110 mmHg. 7. Abnormal muscle enzyme level, defined as CK \> 3 times the upper limit of normal. 8. Active liver disease, including unexplained persistent elevation of serum transaminases, ALT or AST, or elevation of serum transaminases greater than 3 times the upper limit of normal, ALT or AST \> 3 times the upper limit of normal. 4\. Subjects who have received cilostazol within 12 weeks before screening. 5. Subjects who are expected to require any of the following medications during the clinical trial: 1. Lipid-modifying agents other than rosuvastatin administered in this clinical trial, including statins, ezetimibe, bile acid sequestrants, nicotinic acid and its derivatives, and fibrates. However, lipid-modifying agents other than statins are permitted if they have been administered at a stable dose without dose changes for at least 8 weeks from screening, or at least 12 weeks including the run-in period, and no dose change is expected during the clinical trial. 2. Antiplatelet agents, including aspirin, clopidogrel, dipyridamole, indobufen, prasugrel, sarpogrelate, triflusal, ticagrelor, and ticlopidine. However, except for sarpogrelate and ticlopidine, antiplatelet agents are permitted if they have been administered at a stable dose without dose changes for at least 8 weeks from screening, or at least 12 weeks including the run-in period, and no dose change is expected during the clinical trial. Up to two antiplatelet agents other than the investigational product are permitted. If the investigator determines, based on the benefit-risk assessment of the treatment, that monotherapy with one antiplatelet agent or discontinuation is necessary in subjects receiving one or two antiplatelet agents, this may be permitted. 3. Anticoagulants, including heparin, low molecular weight heparin, warfarin, apixaban, dabigatran, edoxaban, and rivaroxaban. However, non-vitamin K oral anticoagulants may be permitted if they have been administered at a stable dose without dose changes for at least 8 weeks from screening, or at least 12 weeks including the run-in period, and no dose change is expected during the clinical trial. Subjects receiving both a non-vitamin K oral anticoagulant and an antiplatelet agent are not eligible to participate. 4. Thrombolytic agents, including streptokinase, tenecteplase, and urokinase. 5. Prostaglandin E1 or I2 and their derivatives, including alprostadil, beraprost, iloprost, and limaprost. 6. Other medications used for peripheral arterial disease, including pentoxifylline and Ginkgo biloba extract. 7. Cyclosporine. 8. Analgesics, including NSAIDs. However, concomitant use is permitted if analgesics are used transiently for the treatment of diseases other than the target clinical disease or for the treatment of adverse events. 6\. Pregnant or lactating women, and women of childbearing potential or men who do not agree to use any of the following reliable contraceptive methods from screening until 30 days after the last dose of the investigational product: 1. Implantation of an intrauterine device or intrauterine system. 2. Sterilization of the subject or the subject's partner. 3. Double-barrier method, including spermicide with condom and contraceptive diaphragm, vaginal sponge, or cervical cap. 7\. Subjects who participated in another clinical trial and received or were treated with an investigational drug or medical device within 12 weeks before screening. 8\. Subjects with known hypersensitivity or allergy to any component of the investigational product or to drugs of a similar class. 9\. Subjects with hereditary problems such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption. 10\. Subjects who are judged by the investigator to be ineligible to participate in the clinical trial for any other reason.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in KPAQ Summary Score at Week 24 | Baseline and Week 24 |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in KPAQ Summary Score at Weeks 4, 8, and 12 | Baseline, Week 4, Week 8, and Week 12 |
| Change From Baseline in KPAQ Domain Scores at Weeks 4, 8, 12, and 24 | Baseline, Week 4, Week 8, Week 12, and Week 24 |
| Change From Baseline in 100-mm VAS Score for Lower Limb Pain at Weeks 4, 8, 12, and 24 | Baseline, Week 4, Week 8, Week 12, and Week 24 |
| Improvement Rate of Lower Limb Ischemic Symptoms at Weeks 4, 8, 12, and 24 | Week 4, Week 8, Week 12, and Week 24 |
| Improvement of Lower Limb Ischemic Symptoms Based on Participant Global Assessment at Weeks 4, 8, 12, and 24 | Week 4, Week 8, Week 12, and Week 24 |
| Change From Baseline in Initial Claudication Distance Using the Treadmill Test at Weeks 12 and 24 | Baseline, Week 12, and Week 24 |
| Change From Baseline in Functional Claudication Distance Using the Treadmill Test at Weeks 12 and 24 | Baseline, Week 12, and Week 24 |
| Change From Baseline in Absolute Claudication Distance Using the Treadmill Test at Weeks 12 and 24 | Baseline, Week 12, and Week 24 |
| Change From Baseline in Ankle-Brachial Index at Weeks 12 and 24 | Baseline, Week 12, and Week 24 |
| Percent Change From Baseline in Lipid Parameters at Weeks 12 and 24 | Baseline, Week 12, and Week 24 |
Countries
South Korea
Outcome results
None listed