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Drug-Drug InteractionPhase 4DPARTNCT04487145

Dihydroartemisinin-Piperaquine in the Context of Antiretroviral Therapy

A Phase 4 study testing Dihydroartemisinin-piperaquine in people with Drug-Drug Interaction and HIV Infection, run by University of California, San Francisco at 2 sites in Uganda.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 3 to 17 yearsHealthy volunteers can take part
Conditions the study is for
Drug-Drug Interaction, HIV Infection
What is being tested?
Dihydroartemisinin-piperaquine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
194 participants
Where
2 sitesUganda
Study dates
23 Nov 2020to 11 Apr 2022
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 to 17 years
  • All sexes
  • Healthy volunteers accepted
  • Child

Who may be able to join

  • 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
Show all 15Show fewer
  • 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.

Who cannot join

  • 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
Show all 29Show fewer
  • 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
  • or of childbearing potential and do not agree to consistent and reliable
  • contraception.
  • The following medications are disallowed within 3 weeks prior to receiving study drug:
  • Carbamazepine
  • Clarithromycin
  • Erythromycin (oral)
  • Ketoconazole
  • Phenobarbital
  • Phenytoin
  • Rifabutin
  • Rifampicin
  • Halofantrine
  • Any other medication known to significantly affect CYP450 metabolism.
  • Grapefruit juice should be avoided during the study due to its potential effects on CYP3A4.

Trial locations and contacts

2 sites in 1 country.

Uganda2 sites
  • Baylor-Uganda Center of Excellence on Mulago Hospital Complex and Masafu General Hospital

    Kampala

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

    Masafu, Busia

Other trials in Uganda

About this study

Official title: DPART Study: Dihydroartemisinin-Piperaquine in the Context of Antiretroviral Therapy

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.

Read the detailed description

The primary goal of the study is to assess the pharmacokinetics (PK) and safety of DP in the setting of co-administration with first-line ART regimens (EFV-, LPV/r- or DTG-based ART) in children without malaria. Up to 190 children will be enrolled in one of the 5 groups: 1, HIV-infected children age 3 - 10 years on LPV/r-based ART (n=20 for signal dose DP, 30 standard 3-dose DP). 2, HIV-infected children age 3 - 10 years on EFV-based ART (n=30), 3, HIV-infected children age 11 - 17 years on DTG-based ART (n=30), 4, HIV-uninfected children age 3-10 years (standard 3-dose DP, n=20 for PK sampling after the 1st dose DP, n=30 for sampling after the 3rd dose DP), 5, HIV-uninfected children age 11-17 years (n=30 children receiving 3-dose DP).

HIV-infected participants will be enrolled from the Baylor Uganda Center of Excellence on the Mulago Hospital Complex, Kampala, Uganda. HIV-uninfected participants will be enrolled from Masafu General Hospital (MGH) complex in Busia, and other clinics in the surrounding area. DP weight-based dosing will follow World Health Organization (WHO) Treatment Guidelines for uncomplicated malaria (April 2015). All HIV-infected participants must be stabilized (i.e. no change in regimen for at least 10 days) on EFV, LPV/r, or DTG + 2 nucleoside reverse transcriptase inhibitors (NRTI). HIV-infected children on LPV/r will be enrolled in two Phases: Phase I participants (Group L1) will receive a single dose of DP to determine the magnitude (PK and safety) of the interaction before 3 doses are evaluated, Phase II participants (Group L3) will receive a 3-dose DP regimen (which consists of 3 days of a once daily DP dose). Phase I results will inform Phase II dosing, as a lower dose of DP over 3 days may be warranted. Phase II will not begin until PK and safety results from Phase I are evaluated. Participants in L1 and L3 will be encouraged to participate sequentially in Phase I and Phase II separated by a minimum 42-day washout period; however different children may be enrolled for the 2 phases. Weight-based dose of dihydroartemisinin-piperaquine (DP): 5- <8kg, 20+160mg; 8- <11kg, 30+240mg; 11- <17kg, 40+320mg; 17- <25kg, 60+480mg; 25- <36kg, 80+640mg; 36- <60kg, 120+960mg; 60-<80kg, 160+1280mg; >80kg, 200+1600mg.

Subjects will undergo an intensive PK study sampling design, which entails multiple venous blood collections in a smaller sample of individuals to accurately estimate drug exposure over time. These studies will be conducted in both HIV-infected and HIV-uninfected participants and will allow the researchers to investigate dihydroartemisinin (DHA) and piperaquine (PQ) PK exposure in the context of EFV-, LPV/r- and DTG-based ART in HIV-uninfected children. Comparisons will be based on an intensive PK design for DP area under the concentration-time curve (AUC) estimations. A sample size of 20 children/adolescents will be needed in groups L1 and C1. A sample size of 30 will be needed for each of the other arms (D3, E3, L3, C3a, and C3b). Sampling will occur up to day 42 in the 3-dose groups given the long half-life of PQ and for 14 or 28 days in the single dose groups. The generation of an AUC will permit robust comparisons so that results will inform treatment guidelines and policy.

Being tested
Dihydroartemisinin-piperaquine
Keywords
Drug drug interaction, HIV, malaria, dihydroartemisinin, piperaquine, lopinavir, ritonavir, efavirenz, dolutegravir, Children
Medical subject headings
HIV Infections, Malaria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dihydroartemisinin-piperaquineDrug

    Also called DP, Duocotexin, Eurartesim, DHA-PQ

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

Study groups in NCT04487145
Study groupRoleWhat they receive
HIV-infected children on EFV-based ART (E3)Experimental30 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.
Receives: Drug: Dihydroartemisinin-piperaquine
HIV-infected children on DTG-based ART (D3)Experimental30 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.
Receives: Drug: Dihydroartemisinin-piperaquine
HIV-infected children on LPV/r-based ART (L3)Experimental30 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.
Receives: Drug: Dihydroartemisinin-piperaquine
HIV-uninfected children (C3a)Active comparator30 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.
Receives: Drug: Dihydroartemisinin-piperaquine
HIV-uninfected children (C3b)Active comparator30 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.
Receives: Drug: Dihydroartemisinin-piperaquine
HIV-uninfected children (C1)Active comparator20 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.
Receives: Drug: Dihydroartemisinin-piperaquine
HIV-infected children on LPV/r-based ART (L1)Experimental20 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
Receives: Drug: Dihydroartemisinin-piperaquine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. AUC0-42day in 3-dose Study

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

    Measured: 42 days

  2. 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.

    Measured: 42 days

  3. AUC0-day28 in 3-dose Study

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

    Measured: day 2-28

  4. Cmax for Piperaquine in 3-dose Study

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

    Measured: day 2-28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jul 2020
  2. Study start23 Nov 2020
  3. Primary completion11 Apr 2022
  4. Study completion11 Apr 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
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).
Masking
None (open label)
Enrolment
194 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04487145
Sponsor's protocol ID
18-26978
Other IDs
2R01HD068174-06A1
Acronym
DPART
Status last verified
Feb 2025
First submitted
17 Jul 2020
Last updated
14 Mar 2025
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Dihydroartemisinin-piperaquine in people with Drug-Drug Interaction and HIV Infection, run by University of California, San Francisco at 2 sites in Uganda.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

AUC0-42day in 3-dose Study (time frame: 42 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Mar 2025.

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