Dolutegravir for younger children: results from the ODYSSEY trial

Dolutegravir (DTG) dosed according to World Health Organization (WHO) weight bands in children weighing 10 kg to 20 kg, achieved similar concentrations to adults and older children. But pharmacokinetic (PK) profiles showed high variability in the 6 kg to 10 kg weight band group.

These findings, from a nested PK sub study of the ODYSSEY trial, using the ViiV Healthcare 5 mg dispersible tablet (DT) formulation, were presented at IAS 2019.

ODYSSEY is a phase 3, randomised, non-inferiority trial comparing DTG-based ART to first- and second-line standard of care in children and adolescents.

Data were shown from children weighing 6 kg to < 20 kg. Children weighing 6 kg to <10kg, 10 kg to <14 kg and 14 kg to < 20 kg received DTG DT at 15 kg (3 tablets), 20 mg (4 tablets) and 25 mg (5 tablets) once-daily dosing, respectively.

DTG DT is approximately 1.6 to 2 times more bioavailable than the adult film coated tablets (FCT).

Target reference values were those achieved in adults receiving DTG 50 mg once-daily and twice-daily with Ctrough being the primary target: 0.83 mg/L (CV 26%) and 2.72 mg/L (CV 70%). The investigators also evaluated individual levels above target EC90 (0.32 mg/L) and/or IC90 (0.06 mg/L).

Sampling was at steady state (at least 7 days) and fasted in children over 10 kg and, where possible, younger children.

Of 41 children enrolled from Zimbabwe, Uganda and South Africa, 34 had evaluable PK curves and were included in the analysis: 11, 10 and 13 in the 6 kg to <10 kg, 10 kg to <14 kg and 14 kg to <20 kg weight bands respectively. The youngest participant was 6 months old and the oldest 2.5 years.

The analysis found that DTG DT in children weighing 10 kg to <14 kg and 14 kg to <20kg, dosed once daily, according to WHO weight bands, achieved similar Ctrough to adults.

But children in the 6 to <10 kg weight band had lower geometric mean (GM) Ctrough, more frequent levels below EC90 (4/11) and PK profiles showed high variability.

Results were also similar to those seen in older children and the IMPAACT P1093 study. [2]

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Further PK data collection is ongoing in children in the 3 kg to <6 kg weight band receiving 5 mg if less than and 10 mg if more than 6 months of age.

Both ODYSSEY and IMPAACT P1093 PK data will be included in submissions to FDA and EMA.

Generic manufacturers are developing dispersible scored 10 mg DTG tablets to accommodate WHO paediatric weight bands with fewer tablets/formulations.