Comparison of the ECG Effects Related to Pharmacokinetic Profile of Chloroquine and Piperaquine

Healthy Clinical Trial

Official title: Comparison of the Electrocardiographic Effects in Relation to Pharmacokinetic Profile of Chloroquine and Piperaquine in Healthy Thai Subjects

Status Completed

Clinical Trial Summary

Chloroquine and piperaquine are the two most widely used antimalarial drugs ever. Hundreds of millions of people have received these drugs. Both are structurally similar and have cardiovascular effect. While there are no concerns over the use of chloroquine, regulatory authorities have suggested restrictions on the use of piperaquine.

We have recently completed a series of cross-over clinical and pharmacokinetic evaluations of chloroquine, piperaquine, pyronaridine and primaquine in healthy subjects. These studied were approved by the ethical committee of FTM. All drugs were well tolerated with no clinically significant ECG changes. Four subjects were in two studies. This offers a unique opportunity to compare the electrocardiographic effects of chloroquine and piperaquine in the same subjects and therefore characterize the concentration-effect relationships, and thus relative safety.

We propose to extend the previous subject study to recruit 16 subjects including those who have received either piperaquine or chloroquine in our previous studies so that 20 subjects received both drugs for a crossover comparison. The blood sampling schedule and electrocardiograms would be exactly the same as previously but would finish at 24 hours.

Clinical Trial Description

The investigator team has recently completed two cross-over clinical and pharmacokinetic evaluations chloroquine and piperaquine in healthy subjects i.e. Study A and Study B.

Study A: Phase 1, Open-Label Study to Evaluate Potential Pharmacokinetic Interaction of Orally Administered Primaquine and Chloroquine in Healthy Thai Adult Subjects

Study B: Open-Label Study to Evaluate Potential Pharmacokinetic Interaction of Orally Administered Primaquine and Dihydroartemisinin-Piperaquine in Healthy Adult Subjects

Four subjects were in both studies. The investigator proposes to extend the previous subject study to recruit 16 subjects including but not limited to those who have received either chloroquine from study A or piperaquine form study B in our previous studies so that 20 subjects received both drugs for a crossover comparison.

Subjects who were previously enrolled into study A that received a single dose of 600 mg chloroquine base will receive a single dose of piperaquine phosphate (in form of 120/960 mg dihydroartemisinin-piperaquine) in this study. The subjects who were previously enrolled into study B that received a single dose of piperaquine phosphate (in form of 120/960 mg dihydroartemisinin-piperaquine) will receive a single dose of 600 mg of chloroquine base in this study.

The investigator team may recruit naive subject in case, the team can't reach total number of 20 subjects.

The total duration for each subject's participation in the study is approximately 3 weeks for subject who challenges only one study drug or 11 weeks for subject who challenges both drugs. ;

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Health Services Research

Related Conditions & MeSH terms

• Healthy

• NCT number: NCT02192944
• Study type: Interventional
• Source: University of Oxford
• Status: Completed
• Phase: Phase 4
• Start date: July 2014
• Completion date: September 2015