Abstracts
3427190
(#24) Dose Proportionality of Novel Once-Daily Lithium Carbonate Extended-Release Bi-Layer Matrix Formulation at 600 and 900 Milligrams in Healthy Adults Under Fed Conditions: A Randomized Crossover Study
Abstract: Purpose: This study evaluated the dose proportionality of novel once-daily (QD) lithium carbonate extended-release (XR) bilayer matrix formulation at 600 mg and 900 mg following a single oral dose under fed conditions in healthy adults. Safety and tolerability were also assessed.
Methods: This open-label, balanced, randomized, two-treatment, four-period, four-sequence crossover study enrolled healthy adults. This analysis evaluated dose proportionality for the 600 mg and 900 mg XR formulation following single-dose administration under fed conditions. Blood samples were collected from 21 subjects for pharmacokinetic (PK) evaluation. Plasma lithium concentrations were quantified using a validated ICP-OES method. Primary PK parameters included Cmax, AUC₀₋ₜ, and AUC₀₋∞. Dose proportionality was concluded if 90% confidence intervals for geometric least squares mean ratios of dose-normalized parameters fell within 80.0%-125.0%. Safety was assessed from the screening period to the end of the study. It included clinical examination, clinical laboratory measures, and monitoring for adverse events.
Results: Twenty-one subjects completed 2 treatment periods. Geometric least squares mean ratios for dose-normalized parameters were 97.65% for Cmax (90% CI: 90.48%-105.39%), 105.63% for AUC₀₋ₜ (90% CI: 102.68%-108.67%), and 104.69% for AUC₀₋∞ (90% CI: 102.39%-107.05%). All 90% CIs were within the 80.0%-125.0% acceptance range, confirming proportional increases in systemic exposure between doses. Both dose levels were well tolerated.
Conclusions: This novel once-daily lithium carbonate extended-release bi-layer matrix formulation demonstrated dose proportionality between 600 mg and 900 mg in healthy adults under fed conditions, supporting predictable pharmacokinetics and flexible dose selection.
Short Description: This open-label, randomized crossover study evaluated the dose proportionality of a novel once-daily lithium carbonate extended-release bi-layer matrix formulation at 600 mg and 900 mg in healthy adults under fed conditions. All 90% confidence intervals for dose-normalized pharmacokinetic parameters fell within the 80.0%-125.0% acceptance range, confirming dose proportionality. Both doses were well tolerated. These findings support predictable pharmacokinetics and flexible dose selection.
Name of Sponsoring Organization(s):
Methods: This open-label, balanced, randomized, two-treatment, four-period, four-sequence crossover study enrolled healthy adults. This analysis evaluated dose proportionality for the 600 mg and 900 mg XR formulation following single-dose administration under fed conditions. Blood samples were collected from 21 subjects for pharmacokinetic (PK) evaluation. Plasma lithium concentrations were quantified using a validated ICP-OES method. Primary PK parameters included Cmax, AUC₀₋ₜ, and AUC₀₋∞. Dose proportionality was concluded if 90% confidence intervals for geometric least squares mean ratios of dose-normalized parameters fell within 80.0%-125.0%. Safety was assessed from the screening period to the end of the study. It included clinical examination, clinical laboratory measures, and monitoring for adverse events.
Results: Twenty-one subjects completed 2 treatment periods. Geometric least squares mean ratios for dose-normalized parameters were 97.65% for Cmax (90% CI: 90.48%-105.39%), 105.63% for AUC₀₋ₜ (90% CI: 102.68%-108.67%), and 104.69% for AUC₀₋∞ (90% CI: 102.39%-107.05%). All 90% CIs were within the 80.0%-125.0% acceptance range, confirming proportional increases in systemic exposure between doses. Both dose levels were well tolerated.
Conclusions: This novel once-daily lithium carbonate extended-release bi-layer matrix formulation demonstrated dose proportionality between 600 mg and 900 mg in healthy adults under fed conditions, supporting predictable pharmacokinetics and flexible dose selection.
Short Description: This open-label, randomized crossover study evaluated the dose proportionality of a novel once-daily lithium carbonate extended-release bi-layer matrix formulation at 600 mg and 900 mg in healthy adults under fed conditions. All 90% confidence intervals for dose-normalized pharmacokinetic parameters fell within the 80.0%-125.0% acceptance range, confirming dose proportionality. Both doses were well tolerated. These findings support predictable pharmacokinetics and flexible dose selection.
Name of Sponsoring Organization(s):
