Insulin glargine biosimilar(Wockhardt Bio AG)

The objective of the study was to compare the pharmacokinetic (PK) and pharmacodynamic (PD) properties of an insulin glargine formulation, Glaritus^® (test) with the innovator's formulation Lantus^® (reference) using the euglycemic clamp technique in a single-dose, double-blind, randomized, two sequences, four-period replicate crossover study in healthy volunteers (n = 40).

Subjects received subcutaneous administration of the insulin glargine (0.4 IU/kg) formulation at two occasions for test and reference and a 20% glucose solution was infused at variable rate to maintain euglycemia for 24 h.

Both PK [area under the plasma concentration time curve (AUC_0-24 h) and maximum insulin concentration (C_max)] and PD endpoints [area under glucose infusion rate time curve (_AUCGIR0-24) and maximum glucose infusion rate (GIR_max)] demonstrated bioequivalence of Glaritus to Lantus with the 90% confidence interval of geometric mean ratio of test to reference entirely contained within 0.80-1.25. Both formulations showed equivalent geometric least-square mean LSM value (0.08 nmol/L) for C_max. The geometric LSM AUC_0-24 h value for Glaritus^® (1.09 h nmol/L) was comparable to Lantus (1.05 h nmol/L). Median T_max values were also identical (12 h for both), and median t1/2 values were also equal (18 h for both). For GIR_Tmax, the difference between the means for the two was not statistically significant. No AEs related to study formulations were reported, and both products were well tolerated.

The test product (Glaritus) was found to be bioequivalent to the reference product (Lantus).

CTRI/2015/06/005890; http://www.ctri.nic.in/ .

Dose accuracy and injection force, representing key parameters of insulin pens, were determined for three pens delivering insulin glargine-based copies, Pen Royale (WR) and DispoPen (WD) for Glaritus® (Wockhardt) and GanLee Pen (GL) for Basalin® (Gan & Lee), compared with pens of the originator, ClikSTAR® (CS) and SoloSTAR® (SS) for Lantus® (Sanofi).

Using the weighing procedure recommended by DIN EN ISO 11608–1:2000, dose accuracy was evaluated based on nonrandomized delivery of low (5 U), mid (30 U), and high (60 U) dosage levels. Injection force was measured by dispensing the maximum dose of insulin (60 U for the GL, WR, and WD; 80 U for the SS and CS) at dose speeds of 6 and 10 U/s.

All tested pens delivered comparable average doses within the DIN EN ISO 11608–1:2000 limits at all dosage levels. The GL revealed a higher coefficient of variation (CV) at 5 U, and the WR and WD had higher CVs at all dosage levels compared with the CS and SS. Injection force was higher for the WR, WD, and GL compared with the CS and SS at both dose speeds. In contrast to the CS and SS with an end-of-content feature, doses exceeding the remaining insulin could be dialed with the WR, GL, and WD and, apparently, dispensed with the WD.

All pens fulfilled the dose accuracy requirements defined by DIN EN ISO 11608–1:2000 standards at all three dosage levels, with the WR, WD, and GL showing higher dosage variability and injection force compared with the SS and CS. Thus, the devices that deliver insulin glargine copies show different performance characteristics compared with the originator.