Pharmacokinetic Study of Multi-dose Chloroquine

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and any serious adverse events, drug concentrations and their relation to adverse events, the proportion of children withdrawn or lost to follow up, the cumulative PCR corrected and uncorrected success and failure rates on day 28 and the proportion of early, late clinical and late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.

Study Overview

• Status: Completed
• Conditions: Malaria
• Intervention / Treatment: Drug: Chloroquine-base 50 mg; Drug: Chloroquine-base 70 mg

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• Guinea-Bissau
  • Bissau, Guinea-Bissau, 1004
    • Projecto de Saúde de Bandim

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 9 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chloroquine-base 50 mg; 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
Active Comparator: Chloroquine-base 70 mg; 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

What is the study measuring?

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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Haemoglobin level	The haemoglobin level will be measured on the the specified days.	On day 0, 3 and 28.
Blood pressure	Will be measures on day 1 at midday and on day 28.	On day 1 and day 28
ECG		Will be measures on day 1 and on last treatment day.

Collaborators and Investigators

• Sponsor: Bandim Health Project
• Investigators: Principal Investigator: Poul-Erik Kofoed, Ph.d, Bandim Health Project

Publications and helpful links

General Publications

• Ursing J, Rombo L, Eksborg S, Larson L, Bruvoll A, Tarning J, Rodrigues A, Kofoed PE. High-Dose Chloroquine for Uncomplicated Plasmodium falciparum Malaria Is Well Tolerated and Causes Similar QT Interval Prolongation as Standard-Dose Chloroquine in Children. Antimicrob Agents Chemother. 2020 Feb 21;64(3):e01846-19. doi: 10.1128/AAC.01846-19. Print 2020 Feb 21.

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: March 16, 2013
• First Submitted That Met QC Criteria: March 19, 2013
• First Posted (Estimate): March 20, 2013

Study Record Updates

• Last Update Posted (Estimate): March 11, 2014
• Last Update Submitted That Met QC Criteria: March 10, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: Plasmodium falciparum; children; pharmacokinetic; malaria; chloroquine
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Physiological Effects of Drugs; Anti-Infective Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Amebicides; Filaricides; Antinematodal Agents; Anthelmintics; Chloroquine; Chloroquine diphosphate
• Other Study ID Numbers: 2013-CQ