Evaluation of Cilostazol in Combination With L-Carnitine
Condition: Peripheral Vascular Disease; Intermittent Claudication; Peripheral Arterial Disease
MeSH terms: Peripheral Arterial Disease; Peripheral Vascular Diseases; Vascular Diseases; Intermittent Claudication
Intervention: Levocarnitine tartrate; cilostazol
Intervention description: Capsule form, 1,002 mg (3 capsules) taken by mouth two times per day (morning and evening). L-carnitine will be taken from Day 0 to Day 180.; Background therapy beginning at 50mg (1 pill) taken by mouth two times per day for two to three weeks. Then 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for one to two weeks.
Randomized therapy will consist of 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for approximately 180 days.
Intervention MeSH terms: Cilostazol
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 164.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: Peripheral Vascular Disease; Peripheral Arterial Disease; Intermittent Claudication; Peak Walking Time; Claudication Onset Time; Cilostazol; Carnitine

Summary:

      The purpose of this study is to see how safe and effective L carnitine taken with cilostazol
      is compared to placebo taken with cilostazol for people with intermittent claudication. A
      second purpose of the study is to see if L-carnitine is absorbed into the blood stream.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The subject is >40 years old.

          -  The subject has a diagnosis of Intermittent Claudication (IC) due to Peripheral Artery
             Disease (PAD).

          -  Ankle brachial index (ABI) < 0.90 in at least one extremity, or if Ankle brachial
             index (ABI)is ≥ 0.90 to ≤ 1.0, a reduction of at least 20% in Ankle brachial index
             (ABI), in at least one extremity, when measured within 1 minute after
             claudication-limiting treadmill testing. If the subject has non-compressible arteries
             then a toe brachial index (TBI) < 0.70 is required in at least one extremity.

          -  Symptoms of Intermittent Claudication (IC)must be stable for at least 3 months prior
             to Screening 1.

          -  Peak Walking Time (PWT) of ≥ 1 to ≤ 12 minutes on a Gardner protocol at Screening 2.

          -  If the subject is currently on statin therapy, they need to have been on statin
             therapy for at least 3 months prior to Screening 1. Subjects who have recently
             discontinued statin therapy must "wash-out" for at least one month prior to Screening
             1.

          -  Tolerance to background therapy of cilostazol (approximately 2 weeks of 50 mg by mouth
             (PO) twice daily (BID), approximately 1 week of 100 mg PO BID) between Screening 2 and
             Baseline Visit.

          -  Subjects must be either male or females that are post-menopausal, surgically incapable
             of bearing children or if they are of childbearing potential must have a negative
             serum pregnancy test at Screening 1 and a negative urine pregnancy test at Day 0 and
             must agree to use double-barrier contraceptive methods until the end of
             investigational therapy (Day 180 Visit).

          -  The subject is able to comply with scheduled visits, treatment plan and laboratory
             tests.

          -  The subject is willing to participate in this study as documented by written informed
             consent.

          -  During the tolerance phase of the Screening period, the subject demonstrates at least
             70% compliance with cilostazol and is willing to continue treatment.

        Exclusion Criteria:

          -  Evidence of critical limb ischemia (CLI) (e.g., ischemic rest pain or ischemic
             ulceration).

          -  The subject has had a major amputation of the leg or any other amputation that limits
             walking ability.

          -  The subject has diabetes mellitus type 1 or poorly controlled diabetes mellitus type 2
             (hemoglobin A1c (HbA1c) > 10).

          -  The subject has had a transient ischemic attack (TIA) or deep vein thrombosis in the
             last 3 months.

          -  The subject has had a stroke within the last 6 months.

          -  The subject has participated in an angiogenic gene therapy study, unless known to be
             given placebo.

          -  The subject has any of the following laboratory parameters at Screening 1:

               -  Alanine aminotransferase (ALT), aspartate aminotransferase (AST) or total
                  bilirubin >3 times the upper limit of normal (ULN)

               -  Serum creatinine >2.5 mg/dL

               -  Hemoglobin (Hb) <10 g/dL

               -  White blood cell (WBC) count <3.0 x 103/µL; or > 15 x 103/µL

               -  Platelet count <100 x 103/µL

          -  The subject walks less than 1 minute at 2 miles per hour (mph), 0% grade as determined
             during the Screening 1 treadmill familiarization.

          -  The subject has clinically significant electrocardiogram (ECG) abnormalities at rest
             or changes during exercise or post-exercise at Screening 2 or Day 0.

          -  The subject has any history or clinical evidence of congestive heart failure (CHF),
             with which the clinician-investigator concurs.

          -  The subject has uncontrolled hypertension (resting blood pressure (BP) > 180/100 mmHg)
             or uncontrolled arrhythmic disorders at Screening 1.

          -  History of coronary or peripheral revascularization within 6 months prior to Screening
             1.

          -  The subject plans to undergo coronary or peripheral revascularization during the
             course of the study.

          -  The subject is currently taking L-carnitine or medication for claudication (including
             pentoxifylline or cilostazol). In this situation, the subject would become eligible
             for Screening 1 after a 6 week washout of the medication.

          -  Subjects currently taking or those who anticipate taking ketoconazole, itraconazole,
             or erythromycin. The subject would become eligible for Screening 1 immediately after
             completion of therapy or discontinuation of the drug(s).

          -  The subject has a known, active malignancy that requires active anti-neoplastic
             therapy. (stable basal cell skin cancer allowed. Cancer being treated soley with
             hormonal therapy is allowed.)

          -  The subject has a severe co-morbidity with an expected survival of less than 2 years.

          -  The subject's Peak Walking Time (PWT) is limited by symptoms other than claudication
             (e.g., shortness of breath (SOB), fatigue, angina, arthritis, etc.). If, in the
             opinion of the investigator, the subject were to improve their Peak Walking Time (PWT)
             from study therapy to the extent that his or her walking would then be limited by a
             symptom other than claudication, the subject should not be enrolled.

          -  The subject has a history of alcohol or other substance abuse within 6 months of
             Screening 1.

          -  The subject has an inability to tolerate oral medication administration.

          -  The subject has a known or suspected allergy to the study medication(s) or class of
             study medication(s) (cilostazol or L-carnitine) to be administered.

          -  The subject has initiated an exercise training program within 3 months of Screening 1,
             has the inability to maintain his or her current level of physical activity throughout
             the study, or the subject plans on enrolling in an exercise training program during
             the study.

          -  The subject plans to change his/her smoking status during the planned duration of this
             study (subjects will be advised that stopping smoking is best for his/her health).

          -  The subject is currently pregnant or breastfeeding.

          -  The subject has received an investigational drug or biological agent within 30 days
             prior to Screening 1.

          -  The subject is currently participating in or plans to enroll in another clinical trial
             during this study.

          -  The subject has any other clinically significant medical or psychiatric condition that
             in the opinion of the Investigator could impact the subject's ability to successfully
             complete this trial.

          -  In the Investigator's opinion, the subject experienced any Adverse Events (AEs) during
             the tolerance phase of the Screening period that present a potential ongoing safety
             concern.