Dihydroartemisinin-Piperaquine in the Context of Antiretroviral Therapy

NCT04487145 | Completed Phase 4 Results

• 2 other identifiers: 18-269782R01HD068174-06A1
• Study Type: interventional
• Target: 194
• Locations: 1 country
• Sites: 2

Brief Summary

Open-label prospective intensive pharmacokinetic study of dihydroartemisinin-piperaquine (DP) in HIV-infected children on efavirenz (EFV)-, lopinavir/ritonavir (LPV/r)-, or dolutegravir (DTG)-based antiretroviral therapy (ART) and HIV-uninfected children not on ART. All children will be malaria-uninfected at the time of enrollment.

Conditions

Drug-Drug Interaction; HIV Infection

Keywords

Drug drug interaction; HIV; malaria; dihydroartemisinin; piperaquine; lopinavir; ritonavir; efavirenz; dolutegravir; Children

Outcome Measures

Primary Outcomes (4)

• AUC0-42day in 3-dose Study

  AUC 0-day42 (from time 0 to 42 days) for piperaquine

  42 days

• QTcF in 3-dose Study

  Safety of 3-dose DP regimens determined via-assessment of mean change in QT intervals from baseline; Here we reported mild adverse event defined as QTc F change\>30ms but \<60ms from baseline.

  42 days

• AUC0-day28 in 3-dose Study

  Area under concentration -time curve from pre-3rd dose to day 28

  day 2-28

• Cmax for Piperaquine in 3-dose Study

  maximal piperaquine concentration post the 3rd dose (day 2-42)

  day 2-28

Other Outcomes (10)

• Cmax for Piperaquine in Single-dose Study

  <24hr

• AUC0-24h for Piperaquine in Single-dose Study

  1 day

• QTcF in Single-dose Safety Study

  28 days

Study Arms (7)

HIV-infected children on EFV-based ART (E3)

EXPERIMENTAL

30 HIV-infected children age 3 - 10 years on EFV-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.

Drug: Dihydroartemisinin-piperaquine

HIV-infected children on DTG-based ART (D3)

EXPERIMENTAL

30 HIV-infected children age 11 - 17 years on DTG-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.

Drug: Dihydroartemisinin-piperaquine

HIV-infected children on LPV/r-based ART (L3)

EXPERIMENTAL

30 HIV-infected children age 3 - 10 years on LPV/r-based ART for at least 10 days will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used.

Drug: Dihydroartemisinin-piperaquine

HIV-uninfected children (C3a)

ACTIVE COMPARATOR

30 HIV-uninfected children age 3-10 years not on ART will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used. PK samples are collected after the 3rd dose. Control group for E3 and L3.

Drug: Dihydroartemisinin-piperaquine

HIV-uninfected children (C3b)

ACTIVE COMPARATOR

30 HIV-uninfected children age 11-17 years not on ART will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used. Control group for D3.

Drug: Dihydroartemisinin-piperaquine

HIV-uninfected children (C1)

ACTIVE COMPARATOR

20 HIV-uninfected children age 3-10 years not on ART will take standard 3 consecutive once-daily oral doses of DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used. PK samples are collected after the 1st dose. Control group for L1.

Drug: Dihydroartemisinin-piperaquine

HIV-infected children on LPV/r-based ART (L1)

EXPERIMENTAL

20 HIV-infected children age 3 - 10 years on LPV/r-based ART for at least 10 days will take one oral dose DP (20/120mg tablets) based on weight per 2015 WHO guidelines for DP. The brand name Duocotexin will be used

Drug: Dihydroartemisinin-piperaquine

Interventions

Dihydroartemisinin-piperaquine DRUG

It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure.

Also known as: DP, Duocotexin, Eurartesim, DHA-PQ

HIV-infected children on DTG-based ART (D3); HIV-infected children on EFV-based ART (E3); HIV-infected children on LPV/r-based ART (L1); HIV-infected children on LPV/r-based ART (L3); HIV-uninfected children (C1); HIV-uninfected children (C3a); HIV-uninfected children (C3b)

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• All participants:
• Agreement to come to clinic for all follow-up PK and safety evaluations
• Provision of informed consent.
• HIV-infected participants:
• Residency within 30km of Mulago Hospital.
• Confirmed HIV infection (confirmed positive rapid HIV test or HIV RNA as per
• Ugandan guidelines).
• On stable EFV-, LPV/r- or DTG-based ART for at least 10 days prior to enrollment.
• Age 3 - 10 years if on EFV-based ART or LPV/r-based ART.
• Age 11 - 17 years if on DTG-based ART.
• HIV-uninfected participants:
• Residency within 30km of Masafu General Hospital
• Confirmed HIV negative test (confirmed positive rapid HIV test or HIV RNA as
• per Ugandan guidelines)
• Age 3 - 17 years.

You may not qualify if:

• History of significant comorbidities such as malignancy, active tuberculosis or
• other active WHO stage 4 disease
• Receipt of any medications known to affect CYP450 metabolism (except ART)
• within 14 days of study enrolment (see 4.2.1)
• Hemoglobin \< 7.0 g/dL
• Current malaria infection or recent treatment with antimalarials within 28 days of
• enrolment.
• Asymptomatic parasitemia detected by microscopy or rapid diagnostic test (RDT)
• History of side effects with DP
• Prior history of cardiac disease (personal or family), baseline corrected QT intervals (QTc) \>450msec, or
• receipt of any cardiotoxic drugs or those known to prolong QT intervals History of
• significant comorbidities such as malignancy, active tuberculosis or other WHO
• stage 4 disease
• Weight \< 6kg
• HIV-infected females on DTG-based ART and age 13-17 years who are pregnant

Sponsors & Collaborators

• University of California, San Francisco: lead
• Yale University: collaborator
• Makerere University: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (2)

Masafu General Hospital (MGH) at Busia District, Eastern Uganda

Masafu, Busia, Uganda

Location

Baylor-Uganda Center of Excellence on Mulago Hospital Complex and Masafu General Hospital

Kampala, Uganda

Location

MeSH Terms

Conditions

HIV Infections; Malaria

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Protozoan Infections; Parasitic Diseases; Mosquito-Borne Diseases; Vector Borne Diseases

Results Point of Contact

• Title: Liusheng Huang(Co-Investigator and Drug Research Unit Co-Director)
• Organization: University of Califronia San Francisco

liusheng.huang@ucsf.edu

415-502-2594

Study Officials

• Francesca Aweeka

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Sunil Parikh

  Yale University

  PRINCIPAL INVESTIGATOR

• Norah Mwebaza

  Makerere University

  PRINCIPAL INVESTIGATOR

• Adeodata Kekitiinwa

  Baylor College of Medicine Children's foundation Uganda

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an open-label prospective pharmacokinetic and safety study of DP and 3 different ART regimens (EFV-, LPV/r- and DTG-based ART) in non-malaria-infected 1) HIV-infected children and 2) HIV uninfected children not on ART (controls).

Study Record Dates

• First Submitted: July 17, 2020
• First Posted: July 27, 2020
• Study Start: November 23, 2020
• Primary Completion: April 11, 2022
• Study Completion: April 11, 2022
• Last Updated: March 14, 2025
• Results First Posted: March 14, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

UG (2)