Clinical trial NCT03836833: Lopinavir/r/ Lamivudine/ Abacavir as an Easy to Use Paediatric Formulation
Official title: Pharmacokinetic, Safety and Acceptability Study of the Abacavir/Lamivudine/Lopinavir/Ritonavir/-30/15/ 40/10mg vs. Lopinavir/Ritonavir 40/10mg Pellets Plus Dual Abacavir/Lamivudine-60/30mg Tablets in HIV Infected Children
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: HIV
Lead sponsor: Drugs for Neglected Diseases
Sponsor class: OTHER
Collaborators: name: UNITAID
name: AMS-PHPT Research Platform (Program for HIV Prevention and Treatment)
name: Joint Clinical Research Centre- Kampala
name: Baylor College of Medicine Childrens Foundation, Uganda
name: Epcentre Centre Mbarara Research Centre
name: Institute of Tropical Medicine, Belgium
First posted: 2019-02-11
Enrollment: 50
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: 0 -12 hours Area under the curve plasma concentration versus time for LPV, ABC and 3TC in the 4-in- formulation
timeFrame: 0-12 hours
Secondary outcomes:
measure: Plasma concentration at 12 hours for LPV in the 4in1 formulation
timeFrame: 12 hours
measure: Peak plasma concentration (Cmax) of LPV, ABC and 3TC with the 4-in-1 formulation.
timeFrame: 3-5 weeks
measure: Concentration time maximum for LPV, ABC and 3TC with the 4-in-1 formulation.
timeFrame: 3-5 weeks
measure: Clearance function for LPV, ABC and 3TC with the 4-in-1 formulation.
timeFrame: 3-5 weeks
measure: 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
timeFrame: 0 - 12 hours
measure: Area under curve plasma concentration versus time (0-12) in the 4-in-1 formulation versus the reference treatment regimen.
timeFrame: 0 - 12 hours
measure: Geometric mean ratio (GMR) of steady state LPV, ABC and 3TC in the 4-in-1 formulation versus the reference treatment regimen.
timeFrame: 0 - 12 hours
measure: Peak plasma concentration in the 4-in-1 formulation versus the reference treatment regimen.
timeFrame: 3-5 weeks
measure: Safety: A description of the proportion of children experiencing an Adverse event or Serious Adverse event binomial distribution compared between the two formulations.
timeFrame: 6-8 weeks
measure: 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
timeFrame: 6-8 weeks
measure: Proportion of children with viral load <1000 copies/ml
timeFrame: 6-8 weeks
measure: Changes in CD4 counts compared to baseline
timeFrame: 6-8 week
measure: Changes in CD4 percentage compared to baseline
timeFrame: 6-8 weeks
measure: Acceptability: Description of factors that affect acceptability of the 4 in1 formulation
timeFrame: 6-8 weeks
Other outcomes:
Locations:
city: Kampala
country: Uganda
facility: Baylor College of Medicine Children's Foundation Uganda
city: Kampala
country: Uganda
facility: Joint Clinical research Centre
city: Mbarara
country: Uganda
facility: Epicentre Mbarara Research Centre
Study officials:
affiliation: Drugs for Neglected Diseases initiative
name: Isabelle Andrieux-Meyer, MD
role: STUDY_DIRECTOR
References: