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

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

Sponsors

Lead Sponsor: Drugs for Neglected Diseases

Collaborator: 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

Source 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.

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.

Overall Status Recruiting
Start Date June 4, 2019
Completion Date December 2019
Primary Completion Date November 2019
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
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 Outcome
Measure Time Frame
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
Area under curve plasma concentration versus time (0-12) in the 4-in-1 formulation versus the reference treatment regimen. 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. 0 - 12 hours
Peak plasma concentration in the 4-in-1 formulation versus the reference treatment regimen. 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. 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 6-8 weeks
Proportion of children with viral load <1000 copies/ml 6-8 weeks
Changes in CD4 counts compared to baseline 6-8 week
Changes in CD4 percentage compared to baseline 6-8 weeks
Acceptability: Description of factors that affect acceptability of the 4 in1 formulation 6-8 weeks
Enrollment 50
Condition
Intervention

Intervention Type: Drug

Intervention Name: ABC/3TC/LPV/r granules (30/15/40/10 mgs)

Description: 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

Intervention Type: Drug

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

Description: 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

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

Gender: All

Minimum Age: N/A

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Isabelle Andrieux-Meyer, MD Study Director Drugs for neglected Diseases initiative
Overall Contact

Last Name: Isabelle Andrieux-Meyer, MD

Phone: +41 22 906 92 68

Email: [email protected]

Location
Facility: Status: Contact:
Baylor College of Medicine Children's Foundation Uganda | Kampala, Uganda Recruiting Prof. Adeodata Kekitiinwa, MBChM, MMeD +256772462686 [email protected]
Joint Clinical research Centre | Kampala, Uganda Recruiting Victor Musiime, MBChB,PhD +256 417 723000 [email protected]
Epicentre Mbarara Research Centre | Mbarara, Uganda Recruiting Prof. Juliet Mwanga, MBChB, MMED +256 793328748 [email protected]
Location Countries

Uganda

Verification Date

May 2019

Responsible Party

Type: Sponsor

Has Expanded Access No
Number Of Arms 2
Arm Group

Label: 4in1 granules

Type: Experimental

Description: 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.

Label: LPV/r Pellets Plus ABC/3TC

Type: Experimental

Description: 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

Acronym LOLIPOP
Patient Data Undecided
Study Design Info

Allocation: Randomized

Intervention Model: Crossover Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov