Safety, tolerability and pharmacokinetics of rilpivirine following administration of a long‐acting formulation in healthy volunteers1. Issue 8 (18th May 2015)

• Record Type: Journal Article
• Authors: Verloes, R; Deleu, S; Niemeijer, N; Crauwels, H; Meyvisch, P; Williams, P
• Is Part Of: HIV medicine. Volume 16:Issue 8(2015:Sep.)
• Page Start: 477
• Page End: 484
• Publication Date: 2015-05-18
• Subjects: HIV infections -- Treatment -- Periodicals; HIV-positive persons -- Periodicals; HIV infections -- Treatment -- Decision making -- Periodicals; 616.9792
• DOI: 10.1111/hiv.12247
• Languages: English
• ISSNs: 1464-2662

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="hiv12247-sec-0001" sec-type="section"> <title>Objectives</title> <p>This phase I healthy volunteer study (NCT01031589) was carried out to investigate the safety/tolerability and pharmacokinetics of a rilpivirine (RPV; TMC278) long‐acting (LA) formulation after single and multiple intramuscular (IM) injections.</p> </sec> <sec id="hiv12247-sec-0002" sec-type="section"> <title>Methods</title> <p>In the first part of the study, which had an open‐label design, a single RPV LA IM injection (300 mg/mL) of 300 (<italic>n</italic> = 6) or 600 (<italic>n</italic> = 5) mg was given to the volunteers. In the second part of the study, which had a double‐blind, randomized, placebo‐controlled design, three RPV LA IM injections (one every 4 weeks) at 1200/600/600 mg (<italic>n</italic> = 6) or placebo (<italic>n</italic> = 2) were given. Safety and local tolerability were monitored. RPV plasma concentrations were analysed up to 28 days after injection or until they were < 20 ng/mL.</p> </sec> <sec id="hiv12247-sec-0003" sec-type="section"> <title>Results</title> <p>Grade 1/2 RPV‐related adverse events in the 300, 600 and 1200/600/600 mg groups were: rash (zero, one and one subject, respectively, the last of whom discontinued participation in the study); musculoskeletal stiffness (three, zero and zero subjects, respectively); injection site reactions (one, two and two subjects, respectively). After one injection of 300, 600 or 1200 mg RPV LA, the mean (standard deviation) maximum plasma concentration was 39 (25), 48 (13) and 140 (16) ng/mL, and the mean (standard deviation) area under the concentration–time curve (28 days) was 17 090 (8907), 25 240 (8184) and 55 350 (13 550) ng h/mL, respectively. RPV pharmacokinetics were largely comparable after the 1200 mg loading dose and both 600 mg injections of RPV LA. The mean (standard deviation) RPV plasma concentration across the 28‐day dosing interval after the last injection in the 1200/600/600 mg group was 79 (19) ng/mL.</p> </sec> <sec id="hiv12247-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Single and multiple IM injections of RPV LA demonstrated favourable local/systemic tolerability in healthy volunteers. RPV pharmacokinetics suggested that clinically relevant plasma concentrations can be achieved with this LA formulation.</p> </sec> </abstract>