Comparison of the ECG Effects Related to Pharmacokinetic Profile of Chloroquine and Piperaquine
Condition: Healthy
Study type: Interventional
Phase: Phase 4

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.
    

Detailed 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.
    

Intervention name(s): Chloroquine; Dihydroartemisinin-piperaquine
Intervention type(s): Drug; Drug
Intervention description(s): Chloroquine base 600 mg single dose. To monitor ECG 12 lead at 0 (pre-dose), 1, 2, 4, 8, 12 and 24 hours after dosing.; Dihydroartemisinin-piperaquine 120/960 mg single dose To monitor ECG 12 lead at: 0 (pre-dose), 1, 2, 4, 8, 12 and 24 hours after dosing.
Intervention MeSH terms: Chloroquine; Piperaquine; Artenimol
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Health Services Research
Keywords: ECG; Pharmacokinetic profile