- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01728961
Pharmacology of Antimalarial Therapy With or Without Antiretroviral Therapy
Pharmacology of Artemisinin-Based Antimalarial Therapy Within the Context of Antiretroviral Therapy
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Anticipated)
Phase
- Phase 4
Contacts and Locations
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age ≥3 to ≤12 years at entry.
- Documentation of HIV-1 infection defined as positive results from two samples collected at different time points. The same method may be used at both time points. All samples tested must be whole blood, serum or plasma.
Subjects ≤ 18 months of age
The first test may be any of the following:
- One HIV DNA Polymerase chain reaction (PCR)
- One HIV RNA (quantitative >5,000 copies/mL or qualitative)
- One HIV culture (prior to August 2009)
- One total HIV nucleic acid
If the first test(s) is positive, a second sample collected and tested using any of the tests listed above (except for qualitative RNA assays) in a laboratory participating in an appropriate external quality assurance program and NIH-approved.
Subjects > 18 months of age
The first test may be any of the following:
- Two rapid antibody tests from different manufacturers or based on different principles and epitopes
- One rapid antibody test AND one [enzyme immunoassay (EIA) OR Western blot (WB) OR immunofluorescence OR chemiluminescence]
- One EIA AND one [WB OR immunofluorescence OR chemiluminescence]
- One HIV DNA PCR
- One HIV RNA (quantitative >5,000 copies/mL or qualitative)
- One HIV culture (prior to August 2009)
- One total HIV nucleic acid
If the first test(s) is positive, a second sample collected and tested using any of the tests listed above (except for qualitative RNA assays) in a laboratory participating in an appropriate external quality assurance program and either CAP/Clinical Laboratory Improvement Amendments (CLIA) approved (for US laboratories) or NIH-approved (for international laboratories).
- Presentation with malaria as indicated by positive smear for malaria parasites along with clinical evidence of infection (fever or history of fever in the past 24 hours) with planned treatment with AL.
- Receiving: (a) NO ARV drugs for at least 4 weeks prior to study entry with no intent to initiate ARVs during the study duration, OR (b) NVP-based combination ARV therapy for at least 4 weeks prior to study entry, with the intent to continue same for duration of the study.
- NOTE: Subjects who are managed with a NVP-based ARV therapy at the time of study enrollment will continue on NVP-based ARV therapy while receiving AL treatment. Children who have NOT met eligibility for ART according to national guidelines (based on known available data at time of enrollment) will be permitted to enroll in the study group of children receiving NO ARV drugs. For this study arm of NO ARV drugs, subjects must not be receiving any ARV drugs currently and they have must not have been on any ARV drugs for at least 4 weeks prior to entry.
- If subject is already on antimalarial medication at time of study entry, no more than 3 doses of either generic AL or brand Coartem® (either standard tablet or the dispersible formulation) may be given prior to study entry. Subjects may have received only the first, second, and/or third dose as a different AL formulation from the study formulation of Coartem® Dispersible. However, the actual dose of artemether and lumefantrine that has been administered MUST be the same as that stipulated by the protocol.
- Female subjects of reproductive potential (having reached menses, or not having reached menopause or not having undergone hysterectomy, bilateral oophorectomy, or tubal ligation) who engage in sexual activity that could lead to pregnancy must agree to avoid pregnancy during the entire 42 day trial and to consistently and appropriately use at least two of the following contraception methods: condoms, diaphragm or cervical cap with spermicide, intrauterine device (IUD), hormonal-based contraception. A list of acceptable methods can be found in the FDA Birth Control Guide accessible at: http://www.fda.gov/womens
- Note: "Female subjects of reproductive potential" is defined as girls who have reached menarche or women who have not been post-menopausal for at least 24 consecutive months (e.g. who have had menses within the preceding 24 months), or have not undergone a sterilization procedure (hysterectomy, bilateral oophorectomy or salpingotomy). If the female subject is not of reproductive potential, she is eligible without requiring contraception.
- Demonstrated ability and willingness to swallow study medications.
- Parent or legal guardian able and willing to provide signed informed consent.
- Ability and willingness to complete study procedures and follow-up at the same study site.
Exclusion Criteria:
- Subjects with ≥ Grade 3 hemoglobin abnormalities (toxicities will be graded by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, dated December 2004, Clarification August 2009, must be used and is available on the Regulatory Support Center (RSC) web site (http://rsc.tech-res.com/safetyandpharmacovigilance/).
- Severe malnutrition will be defined as (i) body mass index (BMI) Z-score< -3 Standard Deviations for children ≥5 years old or (ii) Weight-for-Height <-3 Standard Deviations for children <5 years old. (See Appendix IV).
- Note: Children will be evaluated for malnutrition at the time they present for study enrollment when screening evaluations are performed.
- Receipt of a protease inhibitor or efavirenz (EFV) within 4 weeks prior to study entry.
- Subjects not on ART, but who qualify for ART, according to national guidelines (based on all data available at time of enrollment).
- Use of AL for prior episode of malaria within 6 weeks of study entry.
- Currently receiving an antimalarial drug other than AL.
- Pregnancy or breastfeeding
Signs or evidence of severe malaria. Severe malaria is defined as:
- Unarousable coma (if after convulsion, > 30 minutes)
- OR ANY TWO OF THE FOLLOWING SYMPTOMS:
- Recent febrile convulsions (within 24 hours)
- Altered consciousness (confusion, delirium, psychosis, coma)
- Lethargy
- Unable to drink
- Unable to stand/sit due to weakness
- Severe anemia (Hb < 5.0 gm/dL)
- Respiratory distress (labored breathing at rest)
- Jaundice
- Repeated vomiting that, in the opinion of the investigator, would interfere with oral administration and drug absorption.
- Current treatment for malignancy.
- Known allergy or intolerance to milk products
- In the case where a seemingly eligible participant who is small, has a known or planned blood draw, or will have blood drawn for any reason, such that the total volume blood being drawn over any 8 week period will exceed 9.5 mL/kg. (See Appendix II).
- Any disallowed medications (see Section 4.3) used within 3 weeks of study entry.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: ARM A: AL + NVP -based ARV treatment
AL given to children who test positive for malaria and are already taking NVP as prescribed by their healthcare provider
|
Other Names:
|
Active Comparator: ARM B: AL with No ARV treatment
AL given to children who do not meet national guidelines for beginning ARV treatment
|
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Area under the curve from time zero to last quantifiable concentration (AUC)
Time Frame: NVP PK: At study entry and study day 3, AL PK: At study days 3, 4, 8, and 14
|
Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration
|
NVP PK: At study entry and study day 3, AL PK: At study days 3, 4, 8, and 14
|
Toxicity
Time Frame: At study entry and study days 28 and 42
|
Number of subjects with adverse events of Grade 3 or higher will be recorded
|
At study entry and study days 28 and 42
|
Maximum observed plasma concentration (Cmax)
Time Frame: NVP PK: At study entry and study day 3, AL PK: At study days 3, 4, 8, and 14
|
Maximum observed plasma concentration computed for each individual and then summarized for the strata
|
NVP PK: At study entry and study day 3, AL PK: At study days 3, 4, 8, and 14
|
Minimum observed plasma concentration (Cmin)
Time Frame: NVP PK: At study entry and study day 3, AL PK: At study days 3, 4, 8, and 14
|
Minimum observed plasma concentration computed for each individual and then summarized for the strata
|
NVP PK: At study entry and study day 3, AL PK: At study days 3, 4, 8, and 14
|
Toxicity
Time Frame: At study days 28 and 42
|
Percentage of subjects with adverse events of Grade 3 or higher will be recorded Safety Issue: Yes
|
At study days 28 and 42
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
HIV-1 Viral Load
Time Frame: At study entry and study days 8, 14, and 42
|
Dried Blood Spot (DBS) samples will be collected on all study subjects for HIV-1 viral load measurement.
|
At study entry and study days 8, 14, and 42
|
NVP resistance
Time Frame: At study entry and study day 42
|
Dried Blood Spot (DBS) samples will be collected on all subjects.
Drug resistance testing will only be performed on subjects who show changes in viral load pattern between study entry and study day 42.
|
At study entry and study day 42
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Francesca Aweeka, Pharm.D., IMPAACT/UCSF
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- IMPAACT P1079
- U01AI068632 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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