Abstract
Aims
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).
Methods
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.
Results
Both PK [area under the plasma concentration time curve (AUC0–24 h) and maximum insulin concentration (Cmax)] and PD endpoints [area under glucose infusion rate time curve (AUCGIR0–24) and maximum glucose infusion rate (GIRmax)] 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 Cmax. The geometric LSM AUC0–24 h value for Glaritus® (1.09 h nmol/L) was comparable to Lantus (1.05 h nmol/L). Median Tmax values were also identical (12 h for both), and median t1/2 values were also equal (18 h for both). For GIRTmax, 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.
Conclusions
The test product (Glaritus) was found to be bioequivalent to the reference product (Lantus).
Clinical trial registration number
CTRI/2015/06/005890; http://www.ctri.nic.in/.
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Change history
17 November 2020
Authors would like to correct the error in table��2 of the online published article.
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Acknowledgements
The authors also acknowledge Veeda Clinical Research for conduct of the study, Manipal Acunova for analysis of PK samples and Devdutt Pathare for monitoring the study.
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Contributions
Eliford Ngaimisi contributed to data analysis and manuscript writing. Mathangi Gopalakrishnan contributed to data analysis and manuscript writing. Joga Gobburu contributed to manuscript writing. Prasanna Kumar analyzed and interpreted the data. Ashima Bhatia contributed to the study methodology and procedures and data interpretation, Shraddha Tawade, Mushtaque Mastim, Sridhar Yeshamaina and Manish Shah were involved in study design, data collection, data analysis and interpretation. Maharaja Sahib and Dipak Thakur contributed to the development of bioanalysis method of Glargine. All the authors approved the final draft of the manuscript after critical review and revision.
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Conflict of interest
Prasanna Kumar K M is an advisory board member of Wockhardt, Sanofi, Biocon, Novo- Nordisk and Eli Lilly and has conducted clinical research as PI for the insulin analogs for these companies. Shraddha Tawade, Mushtaque Mastim, Manish Shah, Sridhar Yeshamaina, Maharaja Sahib, Dipak Thakur and Ashima Bhatia are employees of Wockhardt Ltd. Eliford Ngaimisi, Mathangi Gopalakrishnan and Joga Gobburu have no conflict of interest to declare.
Ethical approval
The study was conducted in accordance with the declaration of Helsinki and as per the guidelines formulated by the ICH GCP and the Indian Council of Medical Research (ICMR) for biomedical research on human subjects.
Informed consent
Informed consent was obtained from all individual participants included in the study.
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Bhatia, A., Tawade, S., Mastim, M. et al. Comparative evaluation of pharmacokinetics and pharmacodynamics of insulin glargine (Glaritus®) and Lantus® in healthy subjects: a double-blind, randomized clamp study. Acta Diabetol 55, 461–468 (2018). https://doi.org/10.1007/s00592-018-1113-3
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DOI: https://doi.org/10.1007/s00592-018-1113-3