Pharmacokinetic Study of Multi-dose Chloroquine

Study Overview
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Brief Summary
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Chloroquine (CQ) remains an alternative cheap, safe and widely available drug. Our previous research has shown that double (50 mg/kg) standard dose CQ given in split doses had a 95% efficacy and was well tolerated and safe. Still, safety could be an issue when the dose of CQ is increased. Severe adverse events are caused by high peak concentrations of CQ. Using split doses of CQ avoids high peak concentrations enabling the safe administration of high doses, however, pharmacokinetic data are lacking. Children included in the study will be given 50 mg/kg as split doses over 3 days or 70 mg/kg as split doses over 5 days. Treatment will be observed. Drug concentrations and adverse events will be monitored. On day 1, children and their mother/guardian will be requested to stay at the health centre between 9 am and 6 pm. Fifteen children aged 2-10 years with uncomplicated P. falciparum malaria and fulfilling the inclusion criteria will be recruited into each study arm. Following the end of treatment, the children will be seen on the morning of day 7, 14, 21 and 28. Any child wishing to withdraw during the treatment phase and any child with reparasitaemia during the follow up will be given rescue treatment with arthemeter-lumefantrine or quinine according to treatment guidelines in Guinea-Bissau. Final analysis will include a description of included children, proportions of adverse events and any serious adverse events, drug concentrations and their relation to adverse events, the proportion of children withdrawn or lost to follow up, the cumulative PCR corrected and uncorrected success and failure rates on day 28 and the proportion of early, late clinical and late parasitological treatment failures.

Official Title
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Pharmacokinetic Study of Multi-dose Chloroquine

Conditions
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Malaria

Intervention / Treatment
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* Drug: Chloroquine-base 50 mg
* Drug: Chloroquine-base 70 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 2 years and < 10 years. Mono-infection with P. falciparum detected by microscopy. Parasitemia of 1.000-100.000/µl asexual forms. Axillary temperature ≥ 37.5 ˚C or a history of fever within 24 hours. Ability to swallow oral medication. Ability and willingness to comply with the study protocol. Informed consent from a parent or guardian Exclusion Criteria: Signs or symptoms of severe malaria. Presence of general danger signs in children under 5. Persistent vomiting. Presence of severe malnutrition. Any evidence of chronic disease or acute infection other than malaria. Regular medication which may interfere with antimalarial pharmacokinetics. History of hypersensitivity reactions or contraindications to chloroquine.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 9 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chloroquine-base 50 mg<br>Chloroquine-base 10 mg/kg twice a day for 2 days and 5 mg/kg twice a day for another day. | Drug: Chloroquine-base 50 mg<br> <br> |
| Active Comparator: Chloroquine-base 70 mg<br>Chloroquine-base 10 mg/kg twice a day for 2 days and 5 mg/kg twice a day for another 3 days. | Drug: Chloroquine-base 70 mg<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chloroquine serum concentration | Filterpaper blood samples will be collected in the morning and evening on the days of treatment. On day 1 hourly during daytime. | Twice daily during treatment, on day 1 an additional 8 measurements. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parasitemia | Blood smear for microscopy will be performed in the morning and evening on the days of treatment, and for the 50 mg group on day 3. During follow-uo weekly until day 28. | Twice a day dúring treatment and then weekly until day 28. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Plasmodium falciparum, malaria, chloroquine, pharmacokinetic, children