Bioequivalence of a hybrid pegylated liposomal doxorubicin hydrochloride injection and Caelyxe: A single-dose, randomized, multicenter, open-label, two-period crossover study in patients with advanced ovarian cancer

Objective: To evaluate the bioequivalence of a hybrid pegylated liposomal doxorubicin (PLD) hydrochloride injection with reference product Caelyxe.Methods: This multicenter, open-label, balanced, randomized, two-treatment, two-period, two-sequence, singledose, crossover, bioequivalence study was conducted in female patients aged >= 18 years and <= 75 years with ovarian cancer, whose disease progressed or recurred after platinum-based chemotherapy, and who were scheduled to start PLD therapy. Patients were intravenously infused drugs over 1 h at 50 mg/m2 dose two hours after breakfast on the first day of the chemotherapy cycle in period-I and crossed over to the other arm in periodII (day 29). Pharmacokinetic (PK) analyses were performed using two separate, validated liquid chromatography-mass spectrometry methods for encapsulated and unencapsulated doxorubicin.Results: Both the test and reference formulations were well-tolerated and safe. The pharmacokinetic analysis for both encapsulated and unencapsulated doxorubicin was conducted in 50 patients and PK parameters were found to be comparable between test and reference products. The geometric mean ratios (90% confidence interval) of hybrid PLD/Caelyxe were; maximum measured plasma concentration (Cmax): 91.94-97.28%, area under the plasma concentration versus time from time 0 to t (AUC0-t): 95.19-103.67%, AUC from time 0 to , (AUC0-,): 95.13-103.66% for encapsulated doxorubicin and for unencapsulated doxorubicin Cmax: 92.08-116.46%, AUC0-t: 91.91-108.28%, AUC0-,: 93.45-110.05%.Conclusion: The PLD formulation was found to be bioequivalent to Caelyxe.

Automated summary

This study evaluates the bioequivalence of a hybrid pegylated liposomal doxorubicin (PLD) hydrochloride injection with reference product Caelyx. The results show that the pharmacokinetic parameters of both formulations are comparable, confirming the bioequivalence of the PLD formulation to Caelyx.