This single center, multiple ascending dose study will assess the safety, tolerability, pharmacokinetics and pharmacodynamics of RO4905417 at different doses in healthy volunteers and patients with peripheral arterial disease. Three groups of 10 healthy volunteers will receive RO4905417 (either 3mg/kg, 7mg/kg or 20mg/kg) or placebo iv every 28 days for a total of 3 infusions. In addition, two groups of 6 PAD patients will receive RO4905417 (either 3mg/kg, 7mg/kg) or placebo and 1 group of 20 PAD patients will receive 20mg/kg RO4905417 or placebo iv every 28 days for a total of three infusions. The study will have an adaptive design with ongoing assessment of safety and tolerability prior to initiation of the next dose. All subjects will receive 3 doses of RO4905417 or matching placebo at 28 day intervals. The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.

Inclusion Criteria:

• healthy males and females aged 18-65 years (Arms 1,2,5,6,9,10);
• BMI 18-30kg/m2 (Arms 1,2,5,6,9,10);
• males and females aged 45-75 years with confirmed stable PAD (Arms 3,4,7,8,11,12);
• on a stable dose of statin, aspirin or clopidogrel for at least one month prior to the study (Arms 3,4,7,8,11,12);
• BMI 17.5-35kg/m2 (Arms 3,4,7,8,11,12).

Exclusion Criteria:

• patients with pain at rest and/or local complications;
• history of any cardiovascular event within the previous 6 months;
• treatment with drugs potentially affecting coagulation time or platelet aggregation (except aspirin or clopidogrel);
• evidence of hepatic or renal impairment;
• history of bleeding disorders.