Clinical trial NCT00760565: A Multiple Ascending Dose Study of RO4905417 in Healthy Volunteers and Patients With Peripheral Arterial Disease (PAD).
Official title: A Randomized, Double-Blind, Multiple-Ascending Dose, Placebo-Controlled, Parallel Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO4905417 Following Intravenous Infusion in Healthy Volunteers and Patients With Peripheral Arterial Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Peripheral Arterial Disease (PAD)
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2008-09-26
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Safety: Adverse events; clinical laboratory tests; physical examination; vital signs including ECG.
timeFrame: Throughout study
Secondary outcomes:
measure: Pharmacodynamics: bleeding time; protein/vascular markers
timeFrame: Throughout study
measure: Pharmacokinetics of RO4905417
timeFrame: Throughout study
Other outcomes:
Locations:
city: Gainesville
country: United States
state: Florida
city: Cincinnati
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: San Antonio
country: United States
state: Texas
city: Heidelberg
country: Australia
city: Gatineau
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: