Clinical trial NCT02215824 (phase 1, status: terminated)
Conditions: peripheral arterial disease
ICD codes: A18.2, H11.043, H11.053, H18.463, H35.40, H81.393, I73.9
Drugs: biwh 3, placebo
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion:

          -  Patient must have severe PAOD with Chronic Critical Limb Ischaemia, Fontaine class III
             (ischaemic pain at rest) or IV (tissue ulceration or gangrene) due to atherosclerotic
             disease

          -  Patient must be >= 18 years of age

          -  Patient must give written informed consent

          -  Patient must have a life expectancy of at least six months

        Exclusion:

          -  Transient ischaemic attack (TIA), cerebral vascular accident (CVA), myocardial
             infarction (MI) or episode of unstable angina within the past two months

          -  Ophthalmologic conditions: moderate to severe nonproliferative retinopathy,
             proliferative retinopathy, age related maculopathy with choroidal neovascularisation,
             macular edema, intraocular surgery within the previous 6 months, retinal vein
             occlusion

          -  Presence of a clinically significant disease which in the opinion of the investigator
             may either put the patient at risk because of participation in the study or a disease
             which may influence the result of the study or the patient's ability to participate in
             the study

          -  ECG results outside of the reference range of clinical relevance including, but not
             limited to QTcB > 480 msec, PR interval > 240 msec, QRS interval > 140 msec

          -  History of malignant disease, or a positive result on any of the required cancer
             screening tests, unless a definitive subsequent evaluation for cancer is determined to
             be negative

          -  Patients at increased risk of colorectal cancer, including any of the following (1)
             colorectal cancer pr polyps in a first-degree relative younger than 60 or in two
             first-degree relatives of any age, (2) family history of familial adenomatous
             polyposis or hereditary non-polyposis colon cancer, (3) history of adenomatous polyps,
             or (4) history of chronic inflammatory bowel disease (chronic ulcerative colitis or
             Crohn's disease)

          -  Abnormalities greater than two times the upper limit of normal in any of the following
             laboratory values at Visit 1: alanine-aminotransferase (ALT),
             aspartate-aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline
             phosphatase or lactic dehydrogenase (LDH); abnormalities greater than 1.5 times the
             upper limit of normal of total bilirubin or white blood cell count

          -  Any concurrent infectious disease requiring treatment

          -  Severe renal insufficiency (estimated creatinine clearance < 30 mL/min)

          -  Duffy antigen negative blood type with co-existing moderate to severe renal
             insufficiency (estimated creatinine clearance < 80 mL/min), to avoid potential risk of
             significant increase of monocyte chemoattractant protein-1 (MCP-1) levels

          -  Known glomerulonephritis, even if creatinine clearance is apparently normal

          -  Thrombocytopenia, i.e. platelet count <100,000 cells/μl at Visit 1

          -  History of drug or alcohol abuse within the past 2 two years or active drug or alcohol
             abuse, present alcohol intake more than three drinks per day

          -  Inability to comply with the protocol

          -  Treatment with an investigational drug within 30 days or 5 half-lives, whichever is
             greater before Visit 2

          -  Use of cilostazol if cilostazol therapy was started within 2 months prior to trial
             enrollment, or planned initiation of cilostazol therapy during the trial period.
             Patients who have been on cilostazol for > 2 months prior to enrollment may be
             enrolled

          -  Inability to discontinue the intake of coumadin until after completion of the
             treatment period. Patients who were on coumadin must have an international normalised
             ratio (INR) < 1.8 at Visit 2

          -  Previous enrollment in this trial

          -  Hypersensitivity or allergy to heparin, conventional angiographic contrast dye, or
             magnetic resonance angiography (MRA) contrast

          -  Inability to undergo MRA (e.g. heart pacemaker, artificial heart valve, implanted
             neurostimulator, intrauterine device (IUD), metallic ear implant, implanted port for
             delivering insulin, or other foreign or implanted or metallic objects such as bullet
             fragments, metal plates, pins, screws or staples, joint replacement, or penile
             implant)

          -  Know HIV-infection

          -  Unwillingness to take blood products

          -  Pregnancy (to be excluded by serum and urine beta-human chorionic gonadotropin-test in
             women of childbearing potential) or breast feeding

          -  Female of childbearing potential (not 12 months post-menopausal or surgically
             sterilized) not using one of the following methods of birth control: hormonal
             contraceptives, oral or injectable/implantable