Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03836833
Recruitment Status : Not yet recruiting
First Posted : February 11, 2019
Last Update Posted : March 13, 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

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.


Condition or disease Intervention/treatment Phase
HIV Drug: ABC/3TC/LPV/r granules (30/15/40/10 mgs) Drug: LPV/r Pellets (40/10mgs) plus ABC/3TC (60/30mgs) Phase 1 Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : April 2019
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
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.
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

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 Lopinavir/Ritonavir (40/10mg pellets) plus dual Abacavir/Lamivudine (60/30mg dispersible tablets) administered twice daily for at least 3 weeks.

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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. Changes in CD4 counts compared to baseline [ Time Frame: 6-8 week ]
    Changes in CD4 counts compared to baseline

  13. Changes in CD4 percentage compared to baseline [ Time Frame: 6-8 weeks ]
    Changes in CD4 percentage compared to baseline

  14. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03836833


Contacts
Layout table for location contacts
Contact: Isabelle Andrieux-Meyer, MD +41 22 906 92 68 iandrieux-meyer@dndi.org

Locations
Layout table for location information
Uganda
Baylor College of Medicine Children's Foundation Uganda Not yet recruiting
Kampala, Uganda
Contact: Prof. Adeodata Kekitiinwa, MBChM, MMeD    +256772462686    akekitiinwa@baylor-uganda.org   
Joint Clinical research Centre Not yet recruiting
Kampala, Uganda
Contact: Victor Musiime, MBChB,PhD    +256 417 723000    vmusiime@jcrc.org.ug   
Epicentre Mbarara Research Centre Not yet recruiting
Mbarara, Uganda
Contact: Prof. Juliet Mwanga, MBChB, MMED    +256 793328748    juliet.mwanga@epicentre.msf.org   
Sponsors and Collaborators
Drugs for Neglected Diseases
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
Layout table for investigator information
Study Director: Isabelle Andrieux-Meyer, MD Drugs for neglected Diseases initiative

Layout table for additonal information
Responsible Party: Drugs for Neglected Diseases
ClinicalTrials.gov Identifier: NCT03836833     History of Changes
Other Study ID Numbers: DNDi-4in1-01-PHIV
First Posted: February 11, 2019    Key Record Dates
Last Update Posted: March 13, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
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

Additional relevant MeSH terms:
Layout table for MeSH terms
Lamivudine
Ritonavir
Lopinavir
Abacavir
Dideoxynucleosides
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Antimetabolites