LNG20, a new levonorgestrel intrauterine system, is currently being investigated in a phase 3 study for contraception. The objective was to evaluate levonorgestrel ex vivo release rate over 3 years of LNG20 use.
Levonorgestrel release rate was estimated by comparing the average initial levonorgestrel content and the residual levonorgestrel content of expelled or removed systems. The initial levonorgestrel content analysis was performed on 10 random samples at lot release. The estimated release rate was determined by residual drug content analysis of 74 samples that were removed or expelled during the phase 3 study. Residual drug content analysis was performed on six or more samples in each 90-day interval through 2.5 years and six samples between 2.5 and 3 years. A first-order exponential model was used to determine the average rate of change of levonorgestrel content over time. The best-fit curve for the change in levonorgestrel content over time was used to estimate the release rate at 0, 1, 2, and 3 years.
The average initial levonorgestrel content was 52.0±1.8 mg with an initial release rate of 18.6 micrograms per day. The estimated average release rate at 1, 2, and 3 years of use was 16.3, 14.3, and 12.6 micrograms per day, respectively. The average cumulative release was 6.4, 12.0, and 16.9 mg (12%, 23%, and 33% of the initial loading), respectively.
LNG20 releases levonorgestrel at a rate that is comparable with known intrauterine systems containing 52 mg levonorgestrel.
University of Maryland, Baltimore, MD
Financial Disclosure: Drs. Gopalakrishnan, Liu, and Gobburu received research support from Medicines360. Dr. Creinin received research support from Medicines360 and Merck and has received honoraria and served as a consultant for Merck.