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GSK1265744 Pharmacokinetics in Plasma and Tissue After Single-Dose Long-Acting Injectable Administration in Healthy Subjects

Spreen, William PharmD; Ford, Susan L. PharmD; Chen, Shuguang PhD; Wilfret, David MD; Margolis, David MD; Gould, Elizabeth BS; Piscitelli, Stephen PharmD

JAIDS Journal of Acquired Immune Deficiency Syndromes: December 15th, 2014 - Volume 67 - Issue 5 - p 481–486
doi: 10.1097/QAI.0000000000000301
Clinical Science

Background: GSK1265744 (744) is an HIV-1 integrase inhibitor in clinical development as a long-acting (LA) injectable formulation. This study evaluated plasma and tissue pharmacokinetics after single-dose administration of 744 LA administered by intramuscular (IM) or subcutaneous injections.

Methods: This was a phase I, open-label, 9-cohort, parallel study of 744 in healthy subjects. 744 was administered as a 200 mg/mL nanosuspension at doses of 100–800 mg IM and 100–400 mg subcutaneous.

Results: Eight (6 active and 2 placebo) male and female subjects participated in each of the first 7 cohorts. All 8 subjects, 4 males and 4 females, received active 744 LA in cohorts 8 and 9 and underwent rectal and cervicovaginal tissue sampling, respectively. Plasma pharmacokinetic sampling was performed for a minimum of 12 weeks or until 744 concentrations were ≤0.1 μg/mL. Rectal and cervicovaginal tissue biopsies were performed at weeks 2 and 8 (cohort 8) and weeks 4 and 12 (cohort 9). 744 LA was generally safe and well tolerated after single injections. A majority of subjects reported injection site reactions, all graded as mild in intensity. Plasma concentration–time profiles were prolonged with measureable concentrations up to 52 weeks after dosing. 744 LA 800 mg IM achieved mean concentrations above protein adjusted-IC90 for approximately 16 weeks. Rectal and cervicovaginal tissue concentrations ranged from <8% to 28% of corresponding plasma concentrations.

Conclusions: These data suggest 744 LA injection has potential application as a monthly or less frequent HIV treatment or prevention agent.

GlaxoSmithKline, Research Triangle Park, NC.

Correspondence to: Stephen Piscitelli, PharmD, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709 (e-mail:

Supported by ViiV Healthcare.

All authors are employees of and own stock in GlaxoSmithKline.

Presented in part at the XIX International AIDS Conference, July 22–27, 2012, Washington, DC.

Received April 04, 2014

Accepted July 01, 2014

© 2014 by Lippincott Williams & Wilkins