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

NCT03836833 | Unknown Phase 1 DMC

• 1 other identifier: DNDi-4in1-01-PHIV
• Study Type: interventional
• Estimated enrollment: 50
• Locations: 1 country
• Sites: 3
• Actual (reported): Study Start
• Estimated — date passed: Primary Completion
• Estimated — date passed: Study Completion

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.

Conditions

HIV

Outcome Measures

Primary Outcomes (1)

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

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

  0-12 hours

Secondary Outcomes (14)

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

  12 hours

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

  3-5 weeks

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

  3-5 weeks

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

  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

  0 - 12 hours

Study Arms (2)

4in1 granules

EXPERIMENTAL

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

LPV/r Pellets Plus ABC/3TC

EXPERIMENTAL

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

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

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

Also known as: 4in1 Granules

4in1 granules; LPV/r Pellets Plus ABC/3TC

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

Also known as: L PV/r Pellets Plus ABC/3TC tablets

4in1 granules; LPV/r Pellets Plus ABC/3TC

Eligibility Criteria

• Age: 4 Weeks+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Drugs for Neglected Diseases: lead
• UNITAID: collaborator
• AMS-PHPT Research Platform (Program for HIV Prevention and Treatment): collaborator
• Joint Clinical Research Centre- Kampala: collaborator
• Baylor College of Medicine Childrens Foundation, Uganda: collaborator
• Epcentre Centre Mbarara Research Centre: collaborator
• Institute of Tropical Medicine, Belgium: collaborator

Study Sites (3)

Baylor College of Medicine Children's Foundation Uganda

Kampala, Uganda

RECRUITING

Joint Clinical research Centre

Kampala, Uganda

RECRUITING

Epicentre Mbarara Research Centre

Mbarara, Uganda

RECRUITING

Related Publications (1)

• Rotsaert A, Ogara C, Mwanga-Amumpaire J, Kekitiinwa AR, Musiime V, Najjingo E, Kisitu GP, Nazzinda R, Nambi E, Lee J, Diallo M, Kyomuhendo F, Waweru M, Andrieux-Meyer I, Nostlinger C. Acceptability of a new 4-in-1 Abacavir/Lamivudine/Lopinavir/Ritonavir paediatric fixed-dose combination: the caregiver-child dyads' perspective. Ther Adv Infect Dis. 2023 Mar 21;10:20499361231159993. doi: 10.1177/20499361231159993. eCollection 2023 Jan-Dec.

  PMID: 36968554 DERIVED

Study Officials

• Isabelle Andrieux-Meyer, MD

  Drugs for Neglected Diseases initiative

  STUDY DIRECTOR

Central Study Contacts

Isabelle Andrieux-Meyer, MD

CONTACT

+41 22 906 92 68; iandrieux-meyer@dndi.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2018
• First Posted: February 11, 2019
• Last Updated: June 7, 2019

Study Start

June 4, 2019

Actual (reported)

Primary Completion

November 2019

Estimated — date passed

This estimate has passed. The registry has not confirmed an actual date for this milestone.

Study Completion

December 2019

Estimated — date passed

This estimate has passed. The registry has not confirmed an actual date for this milestone.

Record last verified: 2019-05

Locations

UG (3)