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A high\u2010concentration suspension formulation, cabotegravir 400\u00a0mg\/mL (CAB400\u2010D), was developed to enable less frequent dosing and self\u2010administration. This phase 1, double\u2010blind, randomized study (NCT04484337) evaluated intramuscular (IM) gluteal, subcutaneous (SC) abdominal, and IM thigh CAB400\u2010D injections (200\u2010800\u00a0mg [0.5\u20102.0\u00a0mL]) in adults without HIV, using CAB200 injections as active control. Co\u2010administration with recombinant human hyaluronidase (rHuPH20), topical nonsteroidal anti\u2010inflammatory drug, or topical steroid was evaluated for some SC injections. Pharmacokinetics, adverse events (AEs), and participant\u2010reported outcomes were assessed. Overall, 138 participants were enrolled. Absorption was faster with CAB400\u2010D versus CAB200. Within 4 weeks, CAB400\u2010D plasma exposures were similar across administration routes and higher than those of CAB200. Co\u2010administration with rHuPH20 increased the spontaneous absorption rate of CAB400\u2010D but not CAB200. No deaths or drug\u2010related serious AEs were observed. Five (4%) participants discontinued treatment due to AEs (injection\u2010site reactions [ISRs], n\u00a0=\u00a03 discontinuations). Most (99%) participants experienced \u2265\u00a01 ISR. Participants reported good acceptability of injections. Although CAB400\u2010D injections demonstrated acceptable safety\/tolerability, faster absorption than CAB200 limited potential dosing intervals to monthly dosing. Alternative cabotegravir formulations with longer dosing intervals are under clinical evaluation.<\/jats:p>","DOI":"10.1002\/cpdd.1538","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T07:21:34Z","timestamp":1745911294000},"page":"528-541","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A Randomized Phase 1 Study Evaluating Pharmacokinetics, Safety, and Tolerability of a High\u2010Concentration, Long\u2010Acting Cabotegravir Formulation in Adults Without HIV"],"prefix":"10.1002","volume":"14","author":[{"given":"Kelong","family":"Han","sequence":"first","affiliation":[{"name":"GSK  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Benn","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Sievers","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Dorey","sequence":"additional","affiliation":[{"name":"GSK  Mississauga Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Warwick\u2010Sanders","sequence":"additional","affiliation":[{"name":"GSK  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randa","family":"Hareedy","sequence":"additional","affiliation":[{"name":"GSK  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Harkness","sequence":"additional","affiliation":[{"name":"GSK  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Leemereise","sequence":"additional","affiliation":[{"name":"GSK  Amersfoort the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kjersten","family":"Offenbecker","sequence":"additional","affiliation":[{"name":"GSK  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Donatti","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darin B.","family":"Brimhall","sequence":"additional","affiliation":[{"name":"PPD, Inc.  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