A randomized trial in healthy subjects to assess the bioequivalence of an atazanavir/cobicistat fixed-dose combination tablet versus administration as separate agents

2014 ◽  
Vol 20 (5) ◽  
pp. 493-500 ◽  
Author(s):  
Heather Sevinsky ◽  
Xiaolu Tao ◽  
Reena Wang ◽  
Palanikumar Ravindran ◽  
Karen Sims ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Healthy Subjects ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Combination Tablet ◽  
Dose Combination

scholarly journals Bioequivalence of a Fixed-Dose Combination Tablet of the Complete Two-Drug Regimen of Dolutegravir and Rilpivirine for Treatment of HIV-1 Infection

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Rashmi Mehta ◽  
Allen Wolstenholme ◽  
Kristin Di Lullo ◽  
Caifeng Fu ◽  
Shashidhar Joshi ◽  
...  
Keyword(s):  
Statistical Power ◽  
Drug Regimen ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Combination Tablet ◽  
Reference Treatment ◽  
Dose Combination ◽  
Hiv 1 ◽  
Test Treatment ◽  
Separate Tablets

ABSTRACTA complete 2-drug regimen of dolutegravir at 50 mg and rilpivirine at 25 mg was approved to treat HIV-1 infection in virologically suppressed patients after demonstrating acceptable efficacy and tolerability. This study investigated the bioequivalence and pharmacokinetics of the fixed-dose combination tablet compared with those of separate tablets. Secondary endpoints were the tolerability and safety of the fixed-dose combination tablet. In this open-label, randomized-sequence, 2-way crossover trial, single doses of the fixed-dose combination tablet (the test treatment) and the combination of separate tablets (the reference treatment) were administered to healthy adults after a moderate-fat meal, with a 21-day washout between treatments. Pharmacokinetic samples were collected through 12 days after dosing. The primary endpoints were the area under the plasma concentration-time curve (AUC) and the maximum concentration of drug in plasma (Cmax). The study employed a prespecified sample size reestimation based on a blind midpoint review ofCmaxvariability to update the enrollment size to achieve statistical power. Of 118 participants enrolled, 113 received both treatments and underwent pharmacokinetic assessment. The 90% confidence intervals for the geometric least-squares mean ratios for the AUC from 0 h to infinity, the AUC from 0 h to the last quantifiable measurement, andCmax(test treatment versus reference treatment) were within the bioequivalence range of 0.80 to 1.25 for both drugs, indicating bioequivalence. In this study, a single dose of either treatment was well tolerated overall, with 4% (n= 5) and 3% (n= 3) of participants reporting adverse events considered related to the test and reference treatments, respectively. The dolutegravir-rilpivirine fixed-dose combination tablet is bioequivalent to a combination of separate tablets, and no new safety signals emerged. (This study has been registered at ClinicalTrials.gov under identifier NCT02741557.)

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