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

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ClinicalTrials.gov Identifier: NCT03836833
Recruitment Status : Not yet recruiting
First Posted : February 11, 2019
Last Update Posted : May 21, 2019
Sponsor:
Collaborators:
UNITAID
AMS-PHPT Research Platform (Program for HIV Prevention and Treatment)
Joint Clinical Research Centre- Kampala
Baylor College of Medicine Childrens Foundation, Uganda
Epcentre Centre Mbarara Research Centre
Institute of Tropical Medicine, Belgium
Information provided by (Responsible Party):
Drugs for Neglected Diseases

Tracking Information
First Submitted Date  ICMJE December 13, 2018
First Posted Date  ICMJE February 11, 2019
Last Update Posted Date May 21, 2019
Estimated Study Start Date  ICMJE May 2019
Estimated Primary Completion Date November 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 8, 2019)
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 ]
0 -12 hours Area under the curve plasma concentration versus time for LPV, ABC and 3TC in the 4-in- formulation
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03836833 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 8, 2019)
  • Plasma concentration at 12 hours for LPV in the 4in1 formulation [ Time Frame: 12 hours ]
    Plasma concentration at 12 hours for LPV in the 4in1 formulation
  • Peak plasma concentration (Cmax) of LPV, ABC and 3TC with the 4-in-1 formulation. [ Time Frame: 3-5 weeks ]
    Plasma concentration maximum of LPV, ABC and 3TC with the 4-in-1 formulation.
  • Concentration time maximum for 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.
  • Clearance function 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.
  • 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 ]
    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.
  • 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 ]
    Area under curve plasma concentration 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 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.
  • Peak plasma concentration in the 4-in-1 formulation versus the reference treatment regimen. [ Time Frame: 3-5 weeks ]
    Peak plasma concentration in the 4-in-1 formulation versus the reference treatment regimen.
  • 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: A description of the proportion of children experiencing an Adverse event or Serious Adverse event binomial distribution compared between the two formulations.
  • 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 ]
    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
  • Proportion of children with viral load <1000 copies/ml [ Time Frame: 6-8 weeks ]
    Comparison of proportion of children with viral load less than 1000 copies/ml at baseline and at end of the study.
  • Changes in CD4 counts compared to baseline [ Time Frame: 6-8 week ]
    Changes in CD4 counts compared to baseline
  • Changes in CD4 percentage compared to baseline [ Time Frame: 6-8 weeks ]
    Changes in CD4 percentage compared to baseline
  • Acceptability: Description of factors that affect acceptability of the 4 in1 formulation [ Time Frame: 6-8 weeks ]
    Description of factors that affect acceptability of the 4in1 formulation as reported by the caregivers
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Lopinavir/r/ Lamivudine/ Abacavir as an Easy to Use Paediatric Formulation
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV
Intervention  ICMJE
  • Drug: ABC/3TC/LPV/r granules (30/15/40/10 mgs)

    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

    Other Name: 4in1 Granules
  • Drug: LPV/r Pellets (40/10mgs) plus ABC/3TC (60/30mgs)

    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

    Other Name: L PV/r Pellets Plus ABC/3TC tablets
Study Arms  ICMJE
  • Experimental: 4in1 granules
    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.
    Interventions:
    • Drug: ABC/3TC/LPV/r granules (30/15/40/10 mgs)
    • Drug: LPV/r Pellets (40/10mgs) plus ABC/3TC (60/30mgs)
  • Experimental: LPV/r Pellets Plus ABC/3TC

    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

    Interventions:
    • Drug: ABC/3TC/LPV/r granules (30/15/40/10 mgs)
    • Drug: LPV/r Pellets (40/10mgs) plus ABC/3TC (60/30mgs)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: February 8, 2019)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2019
Estimated Primary Completion Date November 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Isabelle Andrieux-Meyer, MD +41 22 906 92 68 iandrieux-meyer@dndi.org
Listed Location Countries  ICMJE Uganda
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03836833
Other Study ID Numbers  ICMJE DNDi-4in1-01-PHIV
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Drugs for Neglected Diseases
Study Sponsor  ICMJE Drugs for Neglected Diseases
Collaborators  ICMJE
  • UNITAID
  • AMS-PHPT Research Platform (Program for HIV Prevention and Treatment)
  • Joint Clinical Research Centre- Kampala
  • Baylor College of Medicine Childrens Foundation, Uganda
  • Epcentre Centre Mbarara Research Centre
  • Institute of Tropical Medicine, Belgium
Investigators  ICMJE
Study Director: Isabelle Andrieux-Meyer, MD Drugs for neglected Diseases initiative
PRS Account Drugs for Neglected Diseases
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP