Trial Outcomes & Findings for Extended Duration Artemether-lumefantrine Treatment for Malaria in Children (NCT NCT03453840)
NCT ID: NCT03453840
Last Updated: 2025-04-15
Results Overview
Area under the plasma concentration versus time curve (AUC) from time 0 to day 21 for lumefantrine
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
305 participants
Primary outcome timeframe
Study day 0-day21
Results posted on
2025-04-15
Participant Flow
The recruitment started on 2/21/2018 and ended on 07/23/2019 and last follow up date was 09/03/2019. Study location was at Masafu General Hospital. Intensive PK recruitments were completed for all 4 arms: HIV negative 3-day and 5-day arm (n=50 each), HIV positive 3-day and 5-day arm (n=30). Population PK recruitments reached the target for HIV negative arms (n=60 each), but not for HIV-positive arms, because of the lack of HIV positive patients in the study sites.
Participant milestones
| Measure |
HIV-infected 3-day AL
Standard 3-day twice daily (BID) regimen of artemether-lumefantrine for uncomplicated malaria, given over 4 days (Study Days 0, 1, 2 and 3) so that sampling will begin in the morning of day 3. These participants are HIV-infected and stabilized on EFV-based ART.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-infected 5-day AL
Extended 5-day BID regimen of artemether-lumefantrine, given over 6 days (Study Days 0, 1, 2, 3, 4, and 5) so that sampling will begin in the morning of day 5. These participants are HIV-infected and stabilized on EFV-based ART.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-uninfected 3-day AL
Standard 3-day BID regimen of artemether-lumefantrine for uncomplicated malaria, given over 4 days (Study Days 0, 1, 2 and 3) so that sampling will begin in the morning of day 3. These participants are HIV-uninfected.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-uninfected 5-day AL
Extended 5-day BID regimen of artemether-lumefantrine, given over 6 days (Study Days 0, 1, 2, 3, 4, and 5) so that sampling will begin in the morning of day 5. These participants are HIV-uninfected.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
39
|
37
|
115
|
114
|
|
Overall Study
COMPLETED
|
35
|
36
|
110
|
110
|
|
Overall Study
NOT COMPLETED
|
4
|
1
|
5
|
4
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Extended Duration Artemether-lumefantrine Treatment for Malaria in Children
Baseline characteristics by cohort
| Measure |
HIV-infected 3-day AL Intensive PK
n=35 Participants
Standard 3-day twice daily (BID) regimen of artemether-lumefantrine for uncomplicated malaria, given over 4 days (Study Days 0, 1, 2 and 3) so that sampling will begin in the morning of day 3. These participants are HIV-infected and stabilized on EFV-based ART.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-infected 5-day AL Intensive PK
n=36 Participants
Extended 5-day BID regimen of artemether-lumefantrine, given over 6 days (Study Days 0, 1, 2, 3, 4, and 5) so that sampling will begin in the morning of day 5. These participants are HIV-infected and stabilized on EFV-based ART.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-uninfected 3-day AL
n=114 Participants
Standard 3-day BID regimen of artemether-lumefantrine for uncomplicated malaria, given over 4 days (Study Days 0, 1, 2 and 3) so that sampling will begin in the morning of day 3. These participants are HIV-uninfected.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-uninfected 5-day AL
n=113 Participants
Extended 5-day BID regimen of artemether-lumefantrine, given over 6 days (Study Days 0, 1, 2, 3, 4, and 5) so that sampling will begin in the morning of day 5. These participants are HIV-uninfected.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
Total
n=298 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
11.5 years
n=5 Participants
|
10.4 years
n=7 Participants
|
5.3 years
n=5 Participants
|
5.9 years
n=4 Participants
|
6.2 years
n=21 Participants
|
|
Sex: Female, Male
Female
|
21 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
64 Participants
n=5 Participants
|
60 Participants
n=4 Participants
|
160 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
50 Participants
n=5 Participants
|
53 Participants
n=4 Participants
|
138 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
35 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
114 Participants
n=5 Participants
|
113 Participants
n=4 Participants
|
298 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Region of Enrollment
Uganda
|
35 participants
n=5 Participants
|
36 participants
n=7 Participants
|
114 participants
n=5 Participants
|
113 participants
n=4 Participants
|
298 participants
n=21 Participants
|
|
Weight
|
28.4 kg
n=5 Participants
|
25.8 kg
n=7 Participants
|
17.3 kg
n=5 Participants
|
19.1 kg
n=4 Participants
|
20.2 kg
n=21 Participants
|
PRIMARY outcome
Timeframe: Study day 0-day21Population: Intensive PK participants only. Population PK participants are excluded here.
Area under the plasma concentration versus time curve (AUC) from time 0 to day 21 for lumefantrine
Outcome measures
| Measure |
HIV-infected 3-day AL Intensive PK
n=30 Participants
Standard 3-day twice daily (BID) regimen of artemether-lumefantrine for uncomplicated malaria, given over 4 days (Study Days 0, 1, 2 and 3) so that sampling will begin in the morning of day 3. These participants are HIV-infected and stabilized on EFV-based ART.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-infected 5-day AL Intensive PK
n=30 Participants
Extended 5-day BID regimen of artemether-lumefantrine, given over 6 days (Study Days 0, 1, 2, 3, 4, and 5) so that sampling will begin in the morning of day 5. These participants are HIV-infected and stabilized on EFV-based ART.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-uninfected 3-day AL Intensive PK
n=50 Participants
Standard 3-day BID regimen of artemether-lumefantrine for uncomplicated malaria, given over 4 days (Study Days 0, 1, 2 and 3) so that sampling will begin in the morning of day 3. These participants are HIV-uninfected.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-uninfected 5-day AL Intensive PK
n=50 Participants
Extended 5-day BID regimen of artemether-lumefantrine, given over 6 days (Study Days 0, 1, 2, 3, 4, and 5) so that sampling will begin in the morning of day 5. These participants are HIV-uninfected.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
|---|---|---|---|---|
|
AUC0-21d
|
144 hr*ug/mL
Interval 114.0 to 182.0
|
205 hr*ug/mL
Interval 151.0 to 279.0
|
259 hr*ug/mL
Interval 222.0 to 302.0
|
318 hr*ug/mL
Interval 274.0 to 370.0
|
PRIMARY outcome
Timeframe: up to study day 42Population: All participants including intensive and population PK participants.
Recurrent malaria determined by microscopy (thick blood smears), loop mediated isothermal amplification (LAMP), or rapid diagnostic test (RDT).
Outcome measures
| Measure |
HIV-infected 3-day AL Intensive PK
n=36 Participants
Standard 3-day twice daily (BID) regimen of artemether-lumefantrine for uncomplicated malaria, given over 4 days (Study Days 0, 1, 2 and 3) so that sampling will begin in the morning of day 3. These participants are HIV-infected and stabilized on EFV-based ART.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-infected 5-day AL Intensive PK
n=36 Participants
Extended 5-day BID regimen of artemether-lumefantrine, given over 6 days (Study Days 0, 1, 2, 3, 4, and 5) so that sampling will begin in the morning of day 5. These participants are HIV-infected and stabilized on EFV-based ART.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-uninfected 3-day AL Intensive PK
n=114 Participants
Standard 3-day BID regimen of artemether-lumefantrine for uncomplicated malaria, given over 4 days (Study Days 0, 1, 2 and 3) so that sampling will begin in the morning of day 3. These participants are HIV-uninfected.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-uninfected 5-day AL Intensive PK
n=113 Participants
Extended 5-day BID regimen of artemether-lumefantrine, given over 6 days (Study Days 0, 1, 2, 3, 4, and 5) so that sampling will begin in the morning of day 5. These participants are HIV-uninfected.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
|---|---|---|---|---|
|
Recurrent Parasitemia Following Treatment by Day 42 (Recrudescence or New Infection)
|
19 Participants
|
18 Participants
|
80 Participants
|
66 Participants
|
PRIMARY outcome
Timeframe: 0-8hrPopulation: Intensive PK participants only, so the participant number here is different from the numbers in the participant flow module, which includes both intensive and population PK participants.
Area under the plasma concentration versus time curve (AUC) from 0 to 8hr post last dose for artemether (ARM)
Outcome measures
| Measure |
HIV-infected 3-day AL Intensive PK
n=30 Participants
Standard 3-day twice daily (BID) regimen of artemether-lumefantrine for uncomplicated malaria, given over 4 days (Study Days 0, 1, 2 and 3) so that sampling will begin in the morning of day 3. These participants are HIV-infected and stabilized on EFV-based ART.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-infected 5-day AL Intensive PK
n=30 Participants
Extended 5-day BID regimen of artemether-lumefantrine, given over 6 days (Study Days 0, 1, 2, 3, 4, and 5) so that sampling will begin in the morning of day 5. These participants are HIV-infected and stabilized on EFV-based ART.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-uninfected 3-day AL Intensive PK
n=50 Participants
Standard 3-day BID regimen of artemether-lumefantrine for uncomplicated malaria, given over 4 days (Study Days 0, 1, 2 and 3) so that sampling will begin in the morning of day 3. These participants are HIV-uninfected.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-uninfected 5-day AL Intensive PK
n=50 Participants
Extended 5-day BID regimen of artemether-lumefantrine, given over 6 days (Study Days 0, 1, 2, 3, 4, and 5) so that sampling will begin in the morning of day 5. These participants are HIV-uninfected.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
|---|---|---|---|---|
|
AUC0-8h for Artemether
|
64.0 hr*ng/mL
Interval 45.5 to 90.0
|
71.7 hr*ng/mL
Interval 54.8 to 93.8
|
95.8 hr*ng/mL
Interval 77.5 to 118.0
|
78.6 hr*ng/mL
Interval 61.3 to 101.0
|
PRIMARY outcome
Timeframe: 0-8hrPopulation: Intensive PK participants only, so the participant number here is different from the numbers in the participant flow module, which includes both intensive and population PK participants.
Area under the plasma concentration versus time curve (AUC) from time 0 to 8hr post last dose for Dihydroartemisinin (DHA)
Outcome measures
| Measure |
HIV-infected 3-day AL Intensive PK
n=30 Participants
Standard 3-day twice daily (BID) regimen of artemether-lumefantrine for uncomplicated malaria, given over 4 days (Study Days 0, 1, 2 and 3) so that sampling will begin in the morning of day 3. These participants are HIV-infected and stabilized on EFV-based ART.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-infected 5-day AL Intensive PK
n=30 Participants
Extended 5-day BID regimen of artemether-lumefantrine, given over 6 days (Study Days 0, 1, 2, 3, 4, and 5) so that sampling will begin in the morning of day 5. These participants are HIV-infected and stabilized on EFV-based ART.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-uninfected 3-day AL Intensive PK
n=50 Participants
Standard 3-day BID regimen of artemether-lumefantrine for uncomplicated malaria, given over 4 days (Study Days 0, 1, 2 and 3) so that sampling will begin in the morning of day 3. These participants are HIV-uninfected.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-uninfected 5-day AL Intensive PK
n=50 Participants
Extended 5-day BID regimen of artemether-lumefantrine, given over 6 days (Study Days 0, 1, 2, 3, 4, and 5) so that sampling will begin in the morning of day 5. These participants are HIV-uninfected.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
|---|---|---|---|---|
|
AUC0-8h for Dihydroartemisinin
|
109 hr.ng/mL
Interval 83.9 to 142.0
|
95.8 hr.ng/mL
Interval 69.7 to 132.0
|
241 hr.ng/mL
Interval 216.0 to 269.0
|
229 hr.ng/mL
Interval 202.0 to 261.0
|
PRIMARY outcome
Timeframe: 0-21 daysMaximal concentration post last dose for lumefantrine
Outcome measures
| Measure |
HIV-infected 3-day AL Intensive PK
n=30 Participants
Standard 3-day twice daily (BID) regimen of artemether-lumefantrine for uncomplicated malaria, given over 4 days (Study Days 0, 1, 2 and 3) so that sampling will begin in the morning of day 3. These participants are HIV-infected and stabilized on EFV-based ART.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-infected 5-day AL Intensive PK
n=30 Participants
Extended 5-day BID regimen of artemether-lumefantrine, given over 6 days (Study Days 0, 1, 2, 3, 4, and 5) so that sampling will begin in the morning of day 5. These participants are HIV-infected and stabilized on EFV-based ART.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-uninfected 3-day AL Intensive PK
n=50 Participants
Standard 3-day BID regimen of artemether-lumefantrine for uncomplicated malaria, given over 4 days (Study Days 0, 1, 2 and 3) so that sampling will begin in the morning of day 3. These participants are HIV-uninfected.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-uninfected 5-day AL Intensive PK
n=50 Participants
Extended 5-day BID regimen of artemether-lumefantrine, given over 6 days (Study Days 0, 1, 2, 3, 4, and 5) so that sampling will begin in the morning of day 5. These participants are HIV-uninfected.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
|---|---|---|---|---|
|
Cmax for Lumefantrine
|
5065 ng/mL
Interval 3894.0 to 6589.0
|
6027 ng/mL
Interval 4253.0 to 8543.0
|
7236 ng/mL
Interval 6023.0 to 8692.0
|
8450 ng/mL
Interval 7085.0 to 10079.0
|
PRIMARY outcome
Timeframe: 0-8hrMaximal concentration post last dose for artemether
Outcome measures
| Measure |
HIV-infected 3-day AL Intensive PK
n=30 Participants
Standard 3-day twice daily (BID) regimen of artemether-lumefantrine for uncomplicated malaria, given over 4 days (Study Days 0, 1, 2 and 3) so that sampling will begin in the morning of day 3. These participants are HIV-infected and stabilized on EFV-based ART.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-infected 5-day AL Intensive PK
n=30 Participants
Extended 5-day BID regimen of artemether-lumefantrine, given over 6 days (Study Days 0, 1, 2, 3, 4, and 5) so that sampling will begin in the morning of day 5. These participants are HIV-infected and stabilized on EFV-based ART.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-uninfected 3-day AL Intensive PK
n=50 Participants
Standard 3-day BID regimen of artemether-lumefantrine for uncomplicated malaria, given over 4 days (Study Days 0, 1, 2 and 3) so that sampling will begin in the morning of day 3. These participants are HIV-uninfected.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-uninfected 5-day AL Intensive PK
n=50 Participants
Extended 5-day BID regimen of artemether-lumefantrine, given over 6 days (Study Days 0, 1, 2, 3, 4, and 5) so that sampling will begin in the morning of day 5. These participants are HIV-uninfected.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
|---|---|---|---|---|
|
Cmax for Artemether
|
22.4 ng/mL
Interval 15.3 to 32.8
|
23.0 ng/mL
Interval 16.4 to 32.3
|
32.5 ng/mL
Interval 25.4 to 41.5
|
27.3 ng/mL
Interval 20.5 to 36.3
|
PRIMARY outcome
Timeframe: 0-8hrMaximal concentration post last dose for dihydroartimisinin (DHA)
Outcome measures
| Measure |
HIV-infected 3-day AL Intensive PK
n=30 Participants
Standard 3-day twice daily (BID) regimen of artemether-lumefantrine for uncomplicated malaria, given over 4 days (Study Days 0, 1, 2 and 3) so that sampling will begin in the morning of day 3. These participants are HIV-infected and stabilized on EFV-based ART.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-infected 5-day AL Intensive PK
n=30 Participants
Extended 5-day BID regimen of artemether-lumefantrine, given over 6 days (Study Days 0, 1, 2, 3, 4, and 5) so that sampling will begin in the morning of day 5. These participants are HIV-infected and stabilized on EFV-based ART.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-uninfected 3-day AL Intensive PK
n=50 Participants
Standard 3-day BID regimen of artemether-lumefantrine for uncomplicated malaria, given over 4 days (Study Days 0, 1, 2 and 3) so that sampling will begin in the morning of day 3. These participants are HIV-uninfected.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-uninfected 5-day AL Intensive PK
n=50 Participants
Extended 5-day BID regimen of artemether-lumefantrine, given over 6 days (Study Days 0, 1, 2, 3, 4, and 5) so that sampling will begin in the morning of day 5. These participants are HIV-uninfected.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
|---|---|---|---|---|
|
Cmax for Dihydroartemisinin
|
43.8 ng/mL
Interval 33.5 to 57.2
|
34.9 ng/mL
Interval 24.6 to 49.4
|
89.0 ng/mL
Interval 77.4 to 102.0
|
87.9 ng/mL
Interval 75.8 to 102.0
|
SECONDARY outcome
Timeframe: study day 0-42We recorded participants tolerance of AL using the NIH Division of AIDS Adult and Pediatric Toxicity Tables.
Outcome measures
| Measure |
HIV-infected 3-day AL Intensive PK
n=35 Participants
Standard 3-day twice daily (BID) regimen of artemether-lumefantrine for uncomplicated malaria, given over 4 days (Study Days 0, 1, 2 and 3) so that sampling will begin in the morning of day 3. These participants are HIV-infected and stabilized on EFV-based ART.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-infected 5-day AL Intensive PK
n=36 Participants
Extended 5-day BID regimen of artemether-lumefantrine, given over 6 days (Study Days 0, 1, 2, 3, 4, and 5) so that sampling will begin in the morning of day 5. These participants are HIV-infected and stabilized on EFV-based ART.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-uninfected 3-day AL Intensive PK
n=114 Participants
Standard 3-day BID regimen of artemether-lumefantrine for uncomplicated malaria, given over 4 days (Study Days 0, 1, 2 and 3) so that sampling will begin in the morning of day 3. These participants are HIV-uninfected.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-uninfected 5-day AL Intensive PK
n=113 Participants
Extended 5-day BID regimen of artemether-lumefantrine, given over 6 days (Study Days 0, 1, 2, 3, 4, and 5) so that sampling will begin in the morning of day 5. These participants are HIV-uninfected.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
|---|---|---|---|---|
|
Number of Participants With Serious Adverse Events
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: study day 0-42drug resistance will be accessed by molecular markers. Polymorphic markers will be typed using capillary electrophoresis.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: study day 0-42Small-molecule metabolites, including metabolic intermediates, hormones and other signaling molecules, and secondary metabolites will be measured in plasma and reported as fold-change (e.g. infected vs uninfected). This is an exploratory study. The multiple measurements could be aggregated to fold-change.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: study day 0chronic protein-calorie malnutrition resulting in slow linear growth (decreased height-for-age: HFA; stunting).
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: study day 0-42Using Loop-mediated isothermal amplification (LAMP), highly sensitive Rapid Diagnostic Test (HS-RDT), and microscope to diagnose recurrent parasitemia. study day 0-42
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: study day 0acute protein-calorie malnutrition resulting in weight loss or slow weight gain (decreased weight-for-height: WFH; wasting).
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: study day 0weight-for-age is an indicator of nutrition status and decreased weight-for-age reflects the combination of chronic and acute protein-calorie malnutrition.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: study day 0-42At varied time points, blood smears for the determination of parasitemia will be obtained following treatment in 3-day vs 5-day AL regimens.
Outcome measures
Outcome data not reported
Adverse Events
HIV-infected 3-day AL
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
HIV-infected 5-day AL
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
HIV-uninfected 3-day AL
Serious events: 2 serious events
Other events: 0 other events
Deaths: 0 deaths
HIV-uninfected 5-day AL
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
HIV-infected 3-day AL
n=35 participants at risk
Standard 3-day twice daily (BID) regimen of artemether-lumefantrine for uncomplicated malaria, given over 4 days (Study Days 0, 1, 2 and 3) so that sampling will begin in the morning of day 3. These participants are HIV-infected and stabilized on EFV-based ART.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-infected 5-day AL
n=36 participants at risk
Extended 5-day BID regimen of artemether-lumefantrine, given over 6 days (Study Days 0, 1, 2, 3, 4, and 5) so that sampling will begin in the morning of day 5. These participants are HIV-infected and stabilized on EFV-based ART.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-uninfected 3-day AL
n=114 participants at risk
Standard 3-day BID regimen of artemether-lumefantrine for uncomplicated malaria, given over 4 days (Study Days 0, 1, 2 and 3) so that sampling will begin in the morning of day 3. These participants are HIV-uninfected.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
HIV-uninfected 5-day AL
n=113 participants at risk
Extended 5-day BID regimen of artemether-lumefantrine, given over 6 days (Study Days 0, 1, 2, 3, 4, and 5) so that sampling will begin in the morning of day 5. These participants are HIV-uninfected.
Artemether-lumefantrine: Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
hypoglycemia
|
0.00%
0/35 • days 0 to 42
|
0.00%
0/36 • days 0 to 42
|
0.88%
1/114 • Number of events 1 • days 0 to 42
|
0.00%
0/113 • days 0 to 42
|
|
Blood and lymphatic system disorders
anemia
|
0.00%
0/35 • days 0 to 42
|
0.00%
0/36 • days 0 to 42
|
0.88%
1/114 • Number of events 1 • days 0 to 42
|
0.00%
0/113 • days 0 to 42
|
Other adverse events
Adverse event data not reported
Additional Information
Liusheng Huang (Co-Investigator and Drug Research Unit Co-Director)
University of California San Francisco
Phone: 415-502-2594
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place