{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T08:15:58Z","timestamp":1765872958490,"version":"3.48.0"},"reference-count":33,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"unspecified","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Investigator-Initiated Studies Program of Merck Canada Inc","award":["59185"],"award-info":[{"award-number":["59185"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,6,19]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Raltegravir is a potent HIV-integrase strand transfer inhibitor (INSTI). Despite its strong activity against HIV-1 strains resistant to other antiretroviral drug classes, it is usually used in combination with other antiretroviral drugs due to the empirical requirement for anti-HIV drug combinations to ensure effective anti-retroviral therapy (ART). As an early-arriving INSTI, raltegravir is clinically familiar for its safety, tolerability and treatment effectiveness. High-dose calcium carbonate formulated as an antacid (as opposed to a supplement formulation) taken orally together with raltegravir is known to reduce systemic raltegravir exposure due to chelation and reduced absorption. This study aims to assess the effect of daily calcium carbonate antacid as TUMS Ultra Strength (US) administration in lower doses, as currently used for oral calcium supplementation, on the steady-state pharmacokinetics (PKs) of once-daily oral raltegravir.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This is an open-label, three-treatment series in three periods in a single group, fixed-sequence PK study in 12 healthy adult volunteers with HIV on ART. Subjects will take 1200\u2009mg of raltegravir single QD oral dose alone for 7\u2009days (period one), then raltegravir 1200\u2009mg with calcium carbonate 500\u2009mg from day 8 to day 14 (period two) and raltegravir 1200\u2009mg with calcium carbonate 1000\u2009mg from day 15 to day 22 (period three). We will conduct serial PK sampling from observed dosing on days 7, 14 and 21, with 24-hour PK sampling scheduled for days 8, 15 and 22. Follow-up will continue until day 51.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This study will adhere to the ICH GCP Guidelines and the Declaration of Helsinki. Ethics approval was obtained from the Ottawa Health Science Network Research Ethics Board under study ID 20190750\u201301\u2009hour. Informed consent will be obtained from all participants prior to enrolment. This protocol will be published in a peer-reviewed journal prior to the study\u2019s completion and closure. Results generated from this activity will also be reported in a peer-reviewed journal.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04258475\">NCT04258475<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-094384","type":"journal-article","created":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T09:45:18Z","timestamp":1751708718000},"page":"e094384","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Influence of concurrent oral calcium carbonate supplementation on steady-state pharmacokinetics of once daily oral raltegravir in persons with HIV: a protocol for a prospective open-label non-randomised study in Canada"],"prefix":"10.1136","volume":"15","clinical-trial-number":[{"clinical-trial-number":"nct04258475","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5002-9688","authenticated-orcid":false,"given":"Luana Leticia","family":"Teixeira Nunes Porto","sequence":"first","affiliation":[{"name":"Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary-Anne","family":"Doyle","sequence":"additional","affiliation":[{"name":"Ottawa Hospital Research Institute, Ottawa, Ontario, Canada"},{"name":"The Ottawa Hospital, Ottawa, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guijin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Ottawa Hospital Research Institute, Ottawa, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy","family":"Tremblay","sequence":"additional","affiliation":[{"name":"Ottawa Hospital Research Institute, Ottawa, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bashour","family":"Yazji","sequence":"additional","affiliation":[{"name":"Ottawa Hospital Research Institute, Ottawa, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salmaan","family":"Kanji","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada"},{"name":"Department of Pharmacy, The Ottawa Hospital, Ottawa, Ontario, Canada"},{"name":"Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D William","family":"Cameron","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada"},{"name":"Medicine, Division of Infectious Diseases, Ottawa Hospital General Campus, Ottawa, Ontario, Canada"},{"name":"Division of Infectious Diseases, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,7,5]]},"reference":[{"key":"2025121600122749000_15.7.e094384.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1660"},{"key":"2025121600122749000_15.7.e094384.2","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0140-6736(18)32462-0","article-title":"Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicentre, double-blind, randomised, non-inferiority, phase 3 trials","volume":"393","author":"Cahn","year":"2019","journal-title":"Lancet"},{"key":"2025121600122749000_15.7.e094384.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2008.10.012"},{"key":"2025121600122749000_15.7.e094384.4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2011.05972.x"},{"key":"2025121600122749000_15.7.e094384.5","doi-asserted-by":"crossref","unstructured":"Liao C , Wang Q . Authentic HIV-1 integrase inhibitors for the treatment of HIV-1\/AIDS. 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Long-acting cabotegravir + rilpivirine every 2 months: ATLAS-2M week 152 results. 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