Lopinavir/r/ Lamivudine/ Abacavir as an Easy to Use Paediatric Formulation (LOLIPOP)

Drugs for Neglected Diseases

Status and phase: Unknown; Phase 2; Phase 1

Conditions: HIV

Treatments: Drug: LPV/r Pellets (40/10mgs) plus ABC/3TC (60/30mgs); Drug: ABC/3TC/LPV/r granules (30/15/40/10 mgs)

Study type: Interventional

Funder types: Other

Identifiers

NCT03836833

DNDi-4in1-01-PHIV

Details and patient eligibility

About

A phase I/II, open label, randomized crossover pharmacokinetic, safety and acceptability study of the Abacavir/Lamivudine/ Lopinavir/Ritonavir (30/15/ 40/10mg ;4-in-1) Fixed-Dose Combination vs. Lopinavir/Ritonavir (40/10mg pellets) plus dual Abacavir/Lamivudine (60/30mg tablets) in HIV infected Children.

The study is intended to support the adoption of the 4-in-1 by healthcare providers and will provide data that may support its registration in certain countries. The study will be carried out in HIV-infected children in Uganda weighing 3 to 25 kg (inclusive) and unable to swallow tablets and will provide supportive clinical data on the pharmacokinetics, safety, tolerability and acceptability of the 4-in-1.

Full description

The primary objective is to estimate the population average exposure to LPV, ABC and 3TC provided by the 4-in-1 formulation in HIV-infected children dosed per WHO weight bands.

The secondary objectives:

• To determine the proportion of children overall, and within each weight band, with a lopinavir C12 <1.0 mg/L while receiving the 4-in-1 formulation
• To evaluate and compare the safety and tolerability of the 4-in-1 formulation versus a reference treatment regimen.
• To compare the bioavailability of LPV, ABC and 3TC in the 4-in-1 formulation versus a reference treatment regimen.
• To assess post exposure CD4 and viral load
• To assess the factors that contribute to acceptability of the new 4-in-1 formulation.

Enrollment: 50 estimated patients

Sex: All

Ages: 4+ weeks old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Children > 4 weeks old and weighing ≥3 and <25 kg at the time of enrolment

• Past or current documentation of a confirmed diagnosis of HIV infection defined as two positive assays from two different samples. The two results may be in any combination of the following:

• At any age: HIV-1 DNA PCR positive

• Documented past HIV-1 RNA viral load > 1,000 copies/mL plasma

• At any age >18 months of age: HIV-1 antibody reactive on two different rapid tests based on national testing algorithm

• ARV treatment eligible children with LPV-based treatment indication* as defined by country-specific guidelines or the WHO paediatric treatment guidelines and confirmed by the investigator

• HIV RNA viral load <1000 copies/mL (suppressed) at the screening visit*

• Inability to swallow LPV/r tablets

• Parent or guardian able and willing to provide written informed consent.

• For lowest weight band (≥3 and ≤ 5.9kgs) ONLY: under treatment for at least 3 weeks but not more than 12 weeks.

  • Does not apply to the youngest children (≥3 and ≤ 5.9kgs)

Exclusion criteria

• Planned or concurrent use of NNRTIs, integrase inhibitors, entry inhibitors, or Protease Inhibitors (PIs) other than LPV/r.
• Treatment failure with proven resistances to PIs.
• Contraindication to use of PIs
• Clinical condition requiring the use of a prohibited medication (see section 7.6) in association with LPV/r, ABC/3TC (Refer to section 7.2- 7.3 of the IB)
• Pulmonary Tuberculosis and any clinically significant disease or finding during screening that, in the investigator's opinion, would compromise participation in this study.
• Treatment with experimental drugs (except for LPV/r Pellets) for any indication within 30 days prior to study entry
• Anticipated transfer of care to a non-participating health facility during the study period

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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50 participants in 2 patient groups

4in1 granules

Experimental group

Description:

Abacavir/Lamivudine/ Lopinavir/Ritonavir (30/15/ 40/10mg ;4-in-1) Fixed-Dose Combination in granules formulation administered twice daily for at least 3 weeks, Followed by Lopinavir/Ritonavir (40/10mg pellets) plus dual Abacavir/Lamivudine (60/30mg dispersible tablets) administered twice daily for at least 3 weeks.

Treatment:

Drug: ABC/3TC/LPV/r granules (30/15/40/10 mgs)

Drug: LPV/r Pellets (40/10mgs) plus ABC/3TC (60/30mgs)

LPV/r Pellets Plus ABC/3TC

Experimental group

Description:

Lopinavir/Ritonavir (40/10mg pellets) plus dual Abacavir/Lamivudine (60/30mg dispersible tablets) administered twice daily for at least 3 weeks. Followed by Abacavir/Lamivudine/ Lopinavir/Ritonavir (30/15/ 40/10mg ;4-in-1) Fixed-Dose Combination in granules formulation administered twice daily for at least 3 weeks

Treatment:

Drug: ABC/3TC/LPV/r granules (30/15/40/10 mgs)

Drug: LPV/r Pellets (40/10mgs) plus ABC/3TC (60/30mgs)