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

Drugs for Neglected Diseases50 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

HIV

Interventions

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

This is a fixed dose combination. Each capsule contains Lopinavir (40mg), Ritonavir (10mg), Abacavir (30mg) and Lamivudine (15mg) in granules formulation. Dosage according to patient's weight: Between 3 and 5.9kg: 2 capsules twice a day Between 6 and 9.9kg: 3 capsules twice a day Between 10 and 13.9kg: 4 capsules twice a day Between 14 and 19.9kg: 5 capsules twice a day Between 20 and 24.9kg: 6 capsules twice a day

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

Lopinavir/Ritonavir (40/10mg pellets) plus dual Abacavir/Lamivudine (60/30mg dispersible tablets) Dosage according to patient's weight: LPV/r Pellets: Between 3 and 5.9kg: 2 capsules twice a day Between 6 and 9.9kg: 3 capsules twice a day Between 10 and 13.9kg: 4 capsules twice a day Between 14 and 19.9kg: 5 capsules twice a day Between 20 and 24.9kg: 6 capsules twice a day ABC/3TC: Between 3 and 5.9kg: 1 tablet twice a day Between 6 and 9.9kg: 1.5 tablets twice a day Between 10 and 13.9kg: 2 tablets twice a day Between 14 and 19.9kg: 2.5 tablets twice a day Between 20 and 24.9kg: 3 tablets twice a day

Eligibility

Sex: ALLMin age: 4 Weeks

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

0 -12 hours Area under the curve plasma concentration versus time for LPV, ABC and 3TC in the 4-in- formulation

Time frame: 0-12 hours

Secondary Outcomes

Plasma concentration at 12 hours for LPV in the 4in1 formulation

Time frame: 12 hours

Peak plasma concentration (Cmax) of LPV, ABC and 3TC with the 4-in-1 formulation.

Plasma concentration maximum of LPV, ABC and 3TC with the 4-in-1 formulation.

Time frame: 3-5 weeks

Concentration time maximum for LPV, ABC and 3TC with the 4-in-1 formulation.

Time frame: 3-5 weeks

Clearance function for LPV, ABC and 3TC with the 4-in-1 formulation.

Time frame: 3-5 weeks

Geometric mean ratio (GMR) of steady state LPV, ABC and 3TC versus time (0-12) in the 4-in-1 formulation versus the reference treatment regimen

Geometric mean ratio (GMR) of steady state LPV, ABC and 3TC versus time (0-12) in the 4-in-1 formulation versus the reference treatment regimen.

Time frame: 0 - 12 hours

Area under curve plasma concentration versus time (0-12) in the 4-in-1 formulation versus the reference treatment regimen.

Time frame: 0 - 12 hours

Geometric mean ratio (GMR) of steady state LPV, ABC and 3TC in the 4-in-1 formulation versus the reference treatment regimen.

Time frame: 0 - 12 hours

Peak plasma concentration in the 4-in-1 formulation versus the reference treatment regimen.

Time frame: 3-5 weeks

Safety: A description of the proportion of children experiencing an Adverse event or Serious Adverse event binomial distribution compared between the two formulations.

Time frame: 6-8 weeks

Safety: Summary of the number and percent of subjects with documented Grade 3 or higher adverse events; each summary will be conducted overall and by formulation

Time frame: 6-8 weeks

Proportion of children with viral load <1000 copies/ml

Comparison of proportion of children with viral load less than 1000 copies/ml at baseline and at end of the study.

Time frame: 6-8 weeks

Changes in CD4 counts compared to baseline

Time frame: 6-8 week

Changes in CD4 percentage compared to baseline

Time frame: 6-8 weeks

Acceptability: Description of factors that affect acceptability of the 4 in1 formulation

Description of factors that affect acceptability of the 4in1 formulation as reported by the caregivers

Time frame: 6-8 weeks

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

Overview

Conditions

Interventions

Eligibility

Locations (3)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts