Background: Dolutegravir (DTG) 5mg dispersible tablets (DT) are small, child-friendly and allow easy scaling. We describe a pharmacokinetic (PK) substudy of DT DTG in children weighing 6-< 20kg dosed by WHO weight bands (WB) conducted within ODYSSEY, an ongoing phase-III trial of DTG (NCT02259127).
Methods: Children weighing 6-< 10kg, 10-< 14kg, 14-< 20kg received DTG 5mg DT at 15, 20, and 25mg QD, respectively. At steady-state, 24-hour PK profiles (7 samples) were constructed after DTG intake. DTG plasma concentrations were measured by UPLC-MS/MS; Phoenix64 was used for non-compartmental analysis. Results were compared to historical PK parameters from adults taking 50mg DTG filmcoated tablets (FCT) QD or BID, previous ODYSSEY PK data and published data from IMPAACTP1093.
Results: 28 children [29 PK curves] from Zimbabwe and Uganda were included in the analysis. PK results (table 1) from WBs 10-< 14kg and 14-< 20kg were similar to PK data from children receiving same DT doses in IMPAACTP1093, and GM C_trough values were similar to children 20-< 40kg in ODYSSEY on DTG FCT 50mg and adults on 50mg DTG FCT QD. In children 14-< 20kg, exposures were ~1.8-2-fold higher on 25mg DT than 25mg FCT, similar to relative bioavailability of DT/FCT in adults. Our data from the 6-< 10kg WB showed lower GM exposure to DTG compared to IMPAACTP1093 with high variability, and 3 of 8 children had observed C_trough below EC₉₀ (0.32mg/L).
Conclusions: DTG DT in children weighing 10-< 20kg, dosed QD in WHO WBs achieves similar C_trough to adults and older children on the adult DTG dose and young children on DT in IMPAACTP1093. Some children in the 6-< 10kg WB had C_trough levels below EC₉₀, and PK profiles showed high variability in this WB. Further PK data collection in children 3-< 10kg is ongoing and all children are followed up for safety.