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A Model-Based Approach Supporting Abacavir/Dolutegravir/Lamivudine Fixed-Dose Combination Approval in Children Living
Hardik Chandasana1, Ann M Buchanan2, Michael McKenna3
1GSK, Collegeville, PA, USA.
Journal of Clinical Pharmacology
|September 5, 2024
Summary
Model-informed drug development (MIDD) expedited the approval of a fixed-dose combination (FDC) of abacavir, dolutegravir, and lamivudine for treating pediatric HIV-1 patients. This approach ensured similar drug exposure, safety, and efficacy in children as observed in adults.
Area of Science:
- Pharmacology
- Pediatric Medicine
- Drug Development
Background:
- The fixed-dose combination (FDC) TRIUMEQ, containing abacavir (ABC), dolutegravir (DTG), and lamivudine (3TC), was approved for adults and adolescents with HIV-1.
- Prior to March 2022, its indication was limited to patients weighing at least 40 kg, despite individual components being approved for younger children.
- A new dispersible tablet formulation (ABC 60 mg/DTG 5 mg/3TC 30 mg) was developed for pediatric patients weighing 6 kg or more.
Purpose of the Study:
- To demonstrate the utility of a model-informed drug development (MIDD) approach for the expedited approval of the ABC/DTG/3TC FDC in pediatric patients.
- To bridge existing data from individual drug components and formulations to support the FDC's use in children aged 10 kg to <40 kg.
Main Methods:
- Population pharmacokinetic (PK) models were developed for pediatric participants across all three components of the ABC/DTG/3TC FDC.
- These PK models were used for exposure prediction, incorporating relative bioavailability data.
- The models facilitated the extrapolation of safety and efficacy data from single-entity studies to the FDC.
Main Results:
- Predicted plasma exposures for the FDC doses in children were consistent with exposures observed for single entities in pediatric and adult studies.
- The MIDD approach confirmed that the FDC results in similar drug exposure compared to individual components.
- Safety and efficacy observed in single-component studies were adequately extrapolated to the FDC.
Conclusions:
- Model-informed drug development (MIDD) significantly facilitated the expedited approval of the ABC/DTG/3TC FDC for pediatric HIV-1 treatment.
- This approach enabled the use of a child-friendly formulation, improving access to effective HIV-1 therapy for younger populations.
- MIDD plays a crucial role in accelerating the availability of pediatric formulations in HIV-1 treatment.
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