A Multiple Ascending Dose Study of RO4905417 in Healthy Volunteers and Patients With Peripheral Arterial Disease (PAD).

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

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.

Study Overview

• Status: Completed
• Conditions: Peripheral Arterial Disease (PAD)
• Intervention / Treatment: Drug: RO4905417; Drug: RO4905417; Drug: RO4905417; Drug: placebo; Drug: placebo; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Heidelberg, Australia, 3084
• Canada
  • Quebec
    • Gatineau, Quebec, Canada, J8Y 6S9
    • Montreal, Quebec, Canada, H1T 1C8
• United States
  • Florida
    • Gainesville, Florida, United States, 32605
  • Ohio
    • Cincinnati, Ohio, United States, 45219
    • Cincinnati, Ohio, United States, 45227
  • Texas
    • San Antonio, Texas, United States, 78229

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: RO4905417; 3mg/kg iv every 28 days for 3 infusions; Drug: RO4905417; 20mg/kg iv every 28 days for 3 infusions; Drug: RO4905417; 7mg/kg iv every 28 days for 3 infusions
Placebo Comparator: 2	Drug: placebo; 3mg/kg iv every 28 days for 3 infusions; Drug: placebo; 7mg/kg iv every 28 days for 3 infusions; Drug: placebo; 20mg/kg iv every 28 days for 3 infusions
Experimental: 3	Drug: RO4905417; 3mg/kg iv every 28 days for 3 infusions; Drug: RO4905417; 20mg/kg iv every 28 days for 3 infusions; Drug: RO4905417; 7mg/kg iv every 28 days for 3 infusions
Placebo Comparator: 4	Drug: placebo; 3mg/kg iv every 28 days for 3 infusions; Drug: placebo; 7mg/kg iv every 28 days for 3 infusions; Drug: placebo; 20mg/kg iv every 28 days for 3 infusions
Experimental: 5	Drug: RO4905417; 3mg/kg iv every 28 days for 3 infusions; Drug: RO4905417; 20mg/kg iv every 28 days for 3 infusions; Drug: RO4905417; 7mg/kg iv every 28 days for 3 infusions
Placebo Comparator: 6	Drug: placebo; 3mg/kg iv every 28 days for 3 infusions; Drug: placebo; 7mg/kg iv every 28 days for 3 infusions; Drug: placebo; 20mg/kg iv every 28 days for 3 infusions
Experimental: 7	Drug: RO4905417; 3mg/kg iv every 28 days for 3 infusions; Drug: RO4905417; 20mg/kg iv every 28 days for 3 infusions; Drug: RO4905417; 7mg/kg iv every 28 days for 3 infusions
Placebo Comparator: 8	Drug: placebo; 3mg/kg iv every 28 days for 3 infusions; Drug: placebo; 7mg/kg iv every 28 days for 3 infusions; Drug: placebo; 20mg/kg iv every 28 days for 3 infusions
Experimental: 11	Drug: RO4905417; 3mg/kg iv every 28 days for 3 infusions; Drug: RO4905417; 20mg/kg iv every 28 days for 3 infusions; Drug: RO4905417; 7mg/kg iv every 28 days for 3 infusions
Experimental: 9	Drug: RO4905417; 3mg/kg iv every 28 days for 3 infusions; Drug: RO4905417; 20mg/kg iv every 28 days for 3 infusions; Drug: RO4905417; 7mg/kg iv every 28 days for 3 infusions
Placebo Comparator: 10	Drug: placebo; 3mg/kg iv every 28 days for 3 infusions; Drug: placebo; 7mg/kg iv every 28 days for 3 infusions; Drug: placebo; 20mg/kg iv every 28 days for 3 infusions
Placebo Comparator: 12	Drug: placebo; 3mg/kg iv every 28 days for 3 infusions; Drug: placebo; 7mg/kg iv every 28 days for 3 infusions; Drug: placebo; 20mg/kg iv every 28 days for 3 infusions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety: Adverse events; clinical laboratory tests; physical examination; vital signs including ECG.	Throughout study

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacodynamics: bleeding time; protein/vascular markers	Throughout study
Pharmacokinetics of RO4905417	Throughout study

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: September 25, 2008
• First Submitted That Met QC Criteria: September 25, 2008
• First Posted (Estimate): September 26, 2008

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Arterial Disease; Peripheral Vascular Diseases
• Other Study ID Numbers: BP21617