title: Lack of effect of oral cabotegravir on the pharmacokinetics of a levonorgestrel/ethinyl oestradiol-containing oral contraceptive in healthy adult women.
abstract: This study aimed to investigate whether cabotegravir (CAB), an integrase inhibitor in development for treatment and prevention of human immunodeficiency virus-1, influences the pharmacokinetics (PK) of a levonorgestrel (LNG) and ethinyl oestradiol (EO)-containing oral contraceptive (OC) in healthy women.
  
  
  
  In this open-label, fixed-sequence crossover study, healthy female subjects received LNG 0.15 mg/EO 0.03 mg tablet once daily Days 1-10 alone and with oral CAB 30 mg once daily Days 11-21. At the end of each treatment period, subjects underwent predose sampling for concentrations of follicle-stimulating hormone, luteinizing hormone, and progesterone and serial PK sampling for plasma LNG, EO, and CAB concentrations.
  
  
  
  Twenty women were enrolled, and 19 completed the study. One subject was withdrawn due to an adverse event unrelated to study medications. Geometric least squares mean ratios (90% confidence interval) of LNG + CAB vs. LNG alone for LNG area under the plasma concentration-time curve over the dosing interval of duration τ and maximum observed plasma concentration were 1.12 (1.07-1.18) and 1.05 (0.96-1.15), respectively. Geometric least squares mean ratio (90% confidence interval) of EO + CAB vs. EO alone for EO area under the plasma concentration-time curve over the dosing interval of duration τ and maximum observed plasma concentration were 1.02 (0.97-1.08) and 0.92 (0.83-1.03), respectively. Steady-state CAB PK parameters were comparable to historical values. There was no apparent difference in mean luteinizing hormone, follicle-stimulating hormone, and progesterone concentrations between periods. No clinically significant trends in laboratory values, vital signs, or electrocardiography values were observed.
  
  
  
  Repeat doses of oral CAB had no significant effect on LNG/EO PK or pharmacodynamics, which supports CAB coadministration with LNG/EO OCs in clinical practice.
authors.affiliation: ViiV Healthcare, Research Triangle Park, North Carolina, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Trezza
authors.affiliation: PAREXEL International, Research Triangle Park, North Carolina, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Ford
authors.affiliation: PAREXEL International, Research Triangle Park, North Carolina, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Gould
authors.affiliation: PAREXEL International, Research Triangle Park, North Carolina, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Lou
authors.affiliation: PAREXEL International, Research Triangle Park, North Carolina, USA.
authors.forename: Chuyun
authors.initials: C
authors.lastname: Huang
authors.affiliation: Quintiles Drug Research Unit, London, UK.
authors.forename: James M
authors.initials: JM
authors.lastname: Ritter
authors.affiliation: ViiV Healthcare, Research Triangle Park, North Carolina, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Buchanan
authors.affiliation: ViiV Healthcare, Research Triangle Park, North Carolina, USA.
authors.forename: William
authors.initials: W
authors.lastname: Spreen
authors.affiliation: ViiV Healthcare, Research Triangle Park, North Carolina, USA.
authors.forename: Parul
authors.initials: P
authors.lastname: Patel
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D003277:Contraceptives, Oral, Combined / Q000494:pharmacology*; D018592:Cross-Over Studies; D004338:Drug Combinations; D004347:Drug Interactions; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D005260:Female; D043373:Follicle Stimulating Hormone, Human / Q000097:blood; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D064368:Healthy Volunteers; D006801:Humans; D016912:Levonorgestrel / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000097:blood; D011374:Progesterone / Q000097:blood; D011728:Pyridones / Q000494:pharmacology*; D055815:Young Adult; D054659:Diketopiperazines
chemical_list: D003277:Contraceptives, Oral, Combined; D004338:Drug Combinations; D004997:Ethinyl Estradiol; D043373:Follicle Stimulating Hormone, Human; D019428:HIV Integrase Inhibitors; D016912:Levonorgestrel; D007986:Luteinizing Hormone; D011374:Progesterone; D011728:Pyridones; C072593:ethinyl estradiol, levonorgestrel drug combination; C584914:cabotegravir; D054659:Diketopiperazines
keywords: cabotegravir; contraceptive; ethinyl oestradiol; levonorgestrel; pharmacokinetics