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| ID | Type | Description | Link |
|---|---|---|---|
| 2R01HD068174-06A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Yale University | OTHER |
| Makerere University | OTHER |
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dihydroartemisinin-piperaquine | Drug | It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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| Measure | Description | Time Frame |
|---|---|---|
| Cmax for Piperaquine in Single-dose Study | Cmax for piperaquine: Maximal concentration in single-dose study to evaluate Safety | <24hr |
| AUC0-24h for Piperaquine in Single-dose Study | AUC 0-24h (from time 0 to 24h) for piperaquine in single-dose study to evaluate safety. |
Inclusion Criteria:
All participants:
HIV-infected participants:
HIV-uninfected participants:
Exclusion Criteria:
The following medications are disallowed within 3 weeks prior to receiving study drug:
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Masafu General Hospital (MGH) at Busia District, Eastern Uganda | Masafu | Busia | Uganda | |||
| Baylor-Uganda Center of Excellence on Mulago Hospital Complex and Masafu General Hospital |
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Single dose study only enrolled 20 children in L1 and 20 in C1 to evaluate the safety in the context of DP and LPV/r drug-drug interaction, only one dose of DP was given in the treatment group (L1). None of those children were included in the 5 groups in the 3-dose full study. So this is not a two-period design.
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| ID | Title | Description |
|---|---|---|
| FG000 | HIV-uninfected Children (C3a) | 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. Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure. |
| FG001 | HIV-infected Children on LPV/R-based ART (L3) | 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. Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure. |
| FG002 | HIV-infected Children on EFV-based ART (E3) | 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. Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure. |
| FG003 | HIV-uninfected Children (C3b) | 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. Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure. |
| FG004 | HIV-infected Children on DTG-based ART (D3) | 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. Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure. |
| FG005 | HIV-uninfected Children (C1) | 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. |
| FG006 | HIV-infected Children on LPV/R-based ART (L1) | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Single-dose Study for Safety Evaluation |
| |||||||||||||
| 3-dose Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | HIV-infected Children on EFV-based ART (E3) | 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. Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | DTG age upper limit is 17 years, which could be up to 17.9 years as long as the age did not reach 18 years. |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | AUC0-42day in 3-dose Study | AUC 0-day42 (from time 0 to 42 days) for piperaquine | Only five arms in 3-dose study. because C1 and L1 were only for single-dose study to evaluate safety, and those participants were not in 3-dose study, | Posted | Geometric Mean | 95% Confidence Interval | hr.ug/mL | 42 days |
|
42 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | HIV-infected Children on EFV-based ART (E3) | 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. Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| QTcF prolongation | Cardiac disorders | Non-systematic Assessment | mild adverse QTcF changes of >30ms but less than 60ms |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Liusheng Huang(Co-Investigator and Drug Research Unit Co-Director) | University of Califronia San Francisco | 415-502-2594 | liusheng.huang@ucsf.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 22, 2019 | Sep 9, 2024 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Apr 7, 2022 | May 30, 2024 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D008288 | Malaria |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
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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).
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| 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. |
|
| 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. |
|
| 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 |
|
|
| 1 day |
| QTcF in Single-dose Safety Study | Cardiotoxicity associated with PQ is QT interval prolongation. Electrocardiogram (ECG) will be performed to provide data on QT intervals in msec. Reported if QTcF>30ms | 28 days |
| The Association of Malnutrition and PK Exposure of DP in HIV-infected and HIV-uninfected Children | Z-score is the anthropomorphic indicator of malnutrition measured as weight-for age (WFA). Children will be characterized as a) "stunted" but not underweight [i.e. weight for age (WFA) z-score>-2); b) underweight, but not stunted (WFA z-score ≤-2); or c) of normal nutritional status (WFA z-scores >-1).](streamdown:incomplete-link) | 42 days |
| Assess Auto-induction of DHA From Single Dose to 3-doses | DHA AUC0-8hr post the 1st dose is compared to AUC0-8hr post the 3rd dose | 3 days |
| CYP2B6 Pharmacogenetics and Its Impact on EFV PK | To assess prevalence of CYP2B6 pharmacogenetic variants and their impact on EFV PK | 4 days |
| The Association of Anthropomorphic Indicators of Malnutrition Measured as Height-for-age (HFA) Z-score and PK Exposure of DP in HIV-infected and HIV-uninfected Children | Children will be characterized as a) "stunted" but not underweight [i.e. height for age (HFA) z-score ≤-2); b) underweight, but not stunted (HFA z-score>-2); or c) of normal nutritional status (HFA z-scores >-1).](streamdown:incomplete-link) | 42 days |
| The Effects of DP on EFV Pharmacokinetics as Measured by Trough-level (Cmin) of EFV | Compare the trough EFV concentration on day 0 (pre-DP and EFV doses) to day 3 (24hr after DP and EFV doses) | 4 days |
| The Effects of DP on DTG Pharmacokinetics as Measured by Trough-level (Cmin) of DTG | Pre-ART sample to quantify trough of DTG, sampled collected via venipuncture on Day 0, 2, & 3 to allow for comparisons of DTG level. | 4 days |
| The Effects of DP on LPV/r Pharmacokinetics as Measured by Trough-level (Cmin) of LPV/r | Pre-ART sample to quantify trough of LPV/r, sampled collected via venipuncture on Day 0, 2, & 3 to allow for comparisons of LPV/r level. | 4 days |
| Kampala |
| Uganda |
| COMPLETED |
|
| NOT COMPLETED |
|
| BG001 | HIV-infected Children on DTG-based ART (D3) | 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. Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure. |
| BG002 | HIV-infected Children on LPV/R-based ART (L3) | 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. Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure. |
| BG003 | HIV-uninfected Children (C3a) | 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. Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure. |
| BG004 | HIV-uninfected Children (C3b) | 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. Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure. |
| BG005 | HIV-uninfected Children (C1) | 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. |
| BG006 | HIV-infected Children on LPV/R-based ART (L1) | 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. |
| BG007 | Total | Total of all reporting groups |
| Median |
| Inter-Quartile Range |
| years |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Weight | Median | Inter-Quartile Range | kg |
|
| HIV-infected Children on DTG-based ART (D3) |
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. Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure. |
| OG002 | HIV-infected Children on LPV/R-based ART (L3) | 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. Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure. |
| OG003 | HIV-uninfected Children (C3a) | 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. Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure. |
| OG004 | HIV-uninfected Children (C3b) | 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. Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure. |
|
|
| Primary | 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. | We only have five arms in 3-dose study. because C1 and L1 were only for single-dose study to evaluate safety. those participants were not in 3-dose study, | Posted | Count of Participants | Participants | 42 days |
|
|
|
| Primary | AUC0-day28 in 3-dose Study | Area under concentration -time curve from pre-3rd dose to day 28 | We only have five arms in phase 2. because C1 and L1 were only for phase 1 safety evaluation. those participants were not in phase 2 study, | Posted | Geometric Mean | 90% Confidence Interval | hr.ug/mL | day 2-28 |
|
|
|
| Primary | Cmax for Piperaquine in 3-dose Study | maximal piperaquine concentration post the 3rd dose (day 2-42) | We only have five arms in 3-dose study. because C1 and L1 were only for single-dose study to evaluate safety. Those participants were not in 3-dose study, | Posted | Geometric Mean | 90% Confidence Interval | ng/mL | day 2-28 |
|
|
|
| Other Pre-specified | Cmax for Piperaquine in Single-dose Study | Cmax for piperaquine: Maximal concentration in single-dose study to evaluate Safety | C1 and L1 were only for phase 1 safety evaluation, and those participants (n= 20 each arm) were not in phase 2 study, | Posted | Geometric Mean | 95% Confidence Interval | ng/mL | <24hr |
|
|
|
| Other Pre-specified | AUC0-24h for Piperaquine in Single-dose Study | AUC 0-24h (from time 0 to 24h) for piperaquine in single-dose study to evaluate safety. | Phase 1 study for safety evaluation was done with two arms (C1 and L1), and those participants (n= 20 each arm) were not in phase 2 study, | Posted | Geometric Mean | 90% Confidence Interval | hr.ug/mL | 1 day |
|
|
|
| Other Pre-specified | QTcF in Single-dose Safety Study | Cardiotoxicity associated with PQ is QT interval prolongation. Electrocardiogram (ECG) will be performed to provide data on QT intervals in msec. Reported if QTcF>30ms | Single-dose study for safety evaluation was done with two arms (C1 and L1), and those participants (n= 20 each arm) were not in 3-dose full study, | Posted | Count of Participants | Participants | 28 days |
|
|
|
| Other Pre-specified | The Association of Malnutrition and PK Exposure of DP in HIV-infected and HIV-uninfected Children | Z-score is the anthropomorphic indicator of malnutrition measured as weight-for age (WFA). Children will be characterized as a) "stunted" but not underweight [i.e. weight for age (WFA) z-score>-2); b) underweight, but not stunted (WFA z-score ≤-2); or c) of normal nutritional status (WFA z-scores >-1).](streamdown:incomplete-link) | Not Posted | 42 days | Participants |
| Other Pre-specified | Assess Auto-induction of DHA From Single Dose to 3-doses | DHA AUC0-8hr post the 1st dose is compared to AUC0-8hr post the 3rd dose | Not Posted | 3 days | Participants |
| Other Pre-specified | CYP2B6 Pharmacogenetics and Its Impact on EFV PK | To assess prevalence of CYP2B6 pharmacogenetic variants and their impact on EFV PK | Not Posted | 4 days | Participants |
| Other Pre-specified | The Association of Anthropomorphic Indicators of Malnutrition Measured as Height-for-age (HFA) Z-score and PK Exposure of DP in HIV-infected and HIV-uninfected Children | Children will be characterized as a) "stunted" but not underweight [i.e. height for age (HFA) z-score ≤-2); b) underweight, but not stunted (HFA z-score>-2); or c) of normal nutritional status (HFA z-scores >-1).](streamdown:incomplete-link) | Not Posted | 42 days | Participants |
| Other Pre-specified | The Effects of DP on EFV Pharmacokinetics as Measured by Trough-level (Cmin) of EFV | Compare the trough EFV concentration on day 0 (pre-DP and EFV doses) to day 3 (24hr after DP and EFV doses) | Not Posted | 4 days | Participants |
| Other Pre-specified | The Effects of DP on DTG Pharmacokinetics as Measured by Trough-level (Cmin) of DTG | Pre-ART sample to quantify trough of DTG, sampled collected via venipuncture on Day 0, 2, & 3 to allow for comparisons of DTG level. | Not Posted | 4 days | Participants |
| Other Pre-specified | The Effects of DP on LPV/r Pharmacokinetics as Measured by Trough-level (Cmin) of LPV/r | Pre-ART sample to quantify trough of LPV/r, sampled collected via venipuncture on Day 0, 2, & 3 to allow for comparisons of LPV/r level. | Not Posted | 4 days | Participants |
| 0 |
| 30 |
| 0 |
| 30 |
| 1 |
| 30 |
| EG001 | HIV-infected Children on DTG-based ART (D3) | 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. Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure. | 0 | 30 | 0 | 30 | 0 | 30 |
| EG002 | HIV-infected Children on LPV/R-based ART (L3) | 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. Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure. | 0 | 30 | 0 | 30 | 8 | 30 |
| EG003 | HIV-uninfected Children (C3a) | 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. Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure. | 0 | 30 | 0 | 30 | 2 | 30 |
| EG004 | HIV-uninfected Children (C3b) | 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. Dihydroartemisinin-piperaquine: It is expected that efavirenz (EFV), lopinavir/ritonavir (LPV/r), and/or dolutegravir (DTG) will alter DP exposure. | 0 | 30 | 0 | 30 | 0 | 30 |
| EG005 | HIV-uninfected Children (C1) | 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 | 0 | 20 | 0 | 20 | 0 | 20 |
| EG006 | HIV-infected Children on LPV/R-based ART (L1) | 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 . | 0 | 20 | 0 | 20 | 0 | 20 |
|
| iron deficient anemia | Blood and lymphatic system disorders | Non-systematic Assessment | moderate iron deficient anemia (low hemoglobin). |
|
Not provided
Not provided
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D000096724 | Mosquito-Borne Diseases |
| D000079426 | Vector Borne Diseases |