A Phase IV, Open Label, 4-period Cross-over Study to Investigate a Drug Interaction Between Lamivudine and Sorbitol Oral Solutions in Healthy Volunteers
Summary
Lamivudine (3TC) is a nucleoside analogue indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and children. Documented literature elucidates that simultaneous administration of multiple sorbitol-containing products could increase the potential for a significant interaction and may contribute to the lower 3TC exposures. In this study several sorbitol doses (3.2 gram (g), 10.2 g, and 13.4 g solutions) will be administered with lamivudine to investigate dose dependency and mimic the situation where multiple sorbitol-containing antiretroviral medications may be co-administered with lamivudine. It will be open label, randomized, 4-way crossover (by William's design method) design at a single centre. Randomized participants will receive a single dose of each of four treatments after wash out period of minimum 7 days.
Timeline
- Start
- 2016-01-01
- Primary completion
- 2016-03-01
- Completion
- 2016-03-11
Outcome
Met primary endpoint
paper Sorbitol 3.2, 10.2, and 13.4 g decreased lamivudine maximum concentration (Cmax ) by 28%, 52%, and 55% PMID 29150845 ↗
paper and area under the concentration-time curve from time 0 to 24 h (AUC0-24 ) by 20%, 39%, and 44%, respectively. PMID 29150845 ↗
registry A: Lamivudine 300 mg vs D: Lamivudine 300 mg + Sorbitol 13.4 g; Ratio 0.637 (90% CI 0.594 to 0.682); ANCOVA NCT02634073 ↗
registry A: Lamivudine 300 mg vs D: Lamivudine 300 mg + Sorbitol 13.4 g; Ratio 0.454 (90% CI 0.412 to 0.500); ANCOVA NCT02634073 ↗
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Lamivudine | Other / unclassified | 300 mg | — |