A Phase 1 Study to Evaluate the Pharmacokinetics and Safety of Cabotegravir in Patients With Hepatic Impairment and Healthy Matched Controls

Clinical Pharmacology in Drug Development
Jafar Sadik ShaikParul Patel

Abstract

Cabotegravir is an investigational integrase inhibitor in development for the treatment and pre-exposure prophylaxis of HIV-1 infection. Liver disease is a major cause of morbidity and mortality in HIV-infected individuals and can impact the pharmacokinetics (PK) of HIV medications. This phase 1 study evaluated the PK of cabotegravir in individuals with moderate hepatic impairment (n = 8) versus healthy controls (n = 8). Participants received a single oral cabotegravir 30-mg tablet and underwent PK sampling to determine total and unbound plasma cabotegravir concentrations. Calculated geometric least-squares mean ratios (90% confidence intervals) for individuals with hepatic impairment versus healthy controls were 0.73 (0.50-1.06) for AUC0-∞ , 0.69 (0.51-0.93) for Cmax , 1.40 (0.80-2.46) for unbound concentration (CU) 2 hours postdose, 1.55 (0.82-2.94) for CU at 24 hours, 2.14 (1.57-2.90) for unbound fraction (FU) at 2 hours, and 1.90 (1.14-3.18) for FU at 24 hours. Adverse events (AEs) occurred in 2 individuals with hepatic impairment and 3 healthy controls and were grade 1/2 in severity. No participant discontinued because of AEs. Increased FU resulted in a modest decrease in total plasma exposure not considered clinically rel...Continue Reading

References

May 1, 1982·Journal of Clinical Pharmacology·D J GreenblattJ Koch-Weser
Sep 21, 2010·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·Jennifer C Price, Chloe L Thio
Mar 21, 2012·Critical Care : the Official Journal of the Critical Care Forum·Mauro BernardiGiacomo Zaccherini
Jun 13, 2012·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Kazuyuki SuzukiUNKNOWN Japanese Nutritional Study Group for Liver Cirrhosis 2008
May 15, 2013·Antimicrobial Agents and Chemotherapy·Stephen CastellinoPaul M Savina
Apr 23, 2014·Journal of Hepatology·Vicente ArroyoXavier Salvatella
Aug 21, 2014·Journal of Acquired Immune Deficiency Syndromes : JAIDS·William SpreenStephen Piscitelli
Jun 8, 2015·Current Opinion in HIV and AIDS·David A Margolis, Marta Boffito
Jul 3, 2015·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Gary David BowersWilliam R Spreen
Jun 19, 2016·Clinical Pharmacokinetics·Anthony T PodanyCourtney V Fletcher
Dec 13, 2016·Current Opinion in Infectious Diseases·Zaid H Tafesh, Elizabeth C Verna
Jul 26, 2017·Antimicrobial Agents and Chemotherapy·S L FordW Spreen
Jul 27, 2017·Vaccine· World Health Organization

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Citations

Jun 9, 2019·The Journal of Pharmacology and Experimental Therapeutics·Mitesh PatelMaciej J Zamek-Gliszczynski
Oct 24, 2019·Current Opinion in HIV and AIDS·Meredith E ClementRaphael J Landovitz
Nov 26, 2019·Current Opinion in HIV and AIDS·Ronald D'Amico, David A Margolis
Aug 30, 2020·Drugs·Kimberly K ScarsiCourtney V Fletcher

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Methods Mentioned

BETA
biopsy
equilibrium dialysis

Clinical Trials Mentioned

NCT02354950

Software Mentioned

STAT
SAS
Integreview

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