Cardiac Safety of Repeated Doses of Dihydroartemisinin-Piperaquine for the Use in Mass Treatment Campaigns

• Status: Completed
• Trial end date: 2016-02-01
• Target enrollment: 0
• Participant gender: All

Summary

Mass drug administration with antimalarial treatment is a tool that can potentially reduce or totally eliminate malaria parasite infections from a population. Dihydroartemisinin-piperaquine (DHA/PPQ) given monthly for 3 months to the entire population might be a good candidate for mass drug administration because the long acting PPQ exerts a long post-treatment prophylactic effect against reinfection and relapse. The use of a repeated dose of DHA/PPQ could lead to increased PPQ plasma concentrations and increased cardiotoxicity. However, there is no data on a second course of treatment or on safety of the drug administered in repeated monthly doses. The proposed project is a clinical trial to assess the electrocardiographic safety of monthly DHA/PPQ (for 3 days at a time) for 3 months. The investigators aim to assess the safety of the drug to be used monthly in mass treatment campaigns. Recommendations issued from this study will benefit health authorities on Lihir-Island by setting the stage for a possible subsequent campaign to completely eliminate malaria from the whole island. This study could be a crucial step to inform the feasibility of drug-based strategies for eliminating malaria elsewhere in PNG, other Melanesian countries and throughout the world.

• Phase: Phase 3
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Lihir Medical Centre
• Collaborators: Barcelona Institute for Global Health; Papua New Guinea Institute of Medical Research; Walter and Eliza Hall Institute of Medical Research
• Treatments: Artemisinins; Artenimol; Dihydroartemisinin; Piperaquine

Criteria

Inclusion Criteria:

1. Male or female ≥3 years to ≤50 years

2. Good general health by medical history physical examination, baseline electrocardiographs and laboratory tests.

3. No clinically relevant abnormalities in blood pressure and heart rate

4. No clinically relevant abnormalities in 12-lead ECG results*

*Patients with a QTcB or QTcF greater than 450 ms or clinically significant abnormalities of rhythm at Screening are not eligible. Patients with a pre-dose baseline value > 450 ms should be withdrawn from the study prior to dosing.

Exclusion Criteria:

5. A history of additional risk factors for Torsades-des-Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome);

6. The use of concomitant medications that prolong the QT/QTc interval;

7. Any condition requiring regular concomitant medication, including herbal products and over-the-counter (OTC) medication or predicted need of any concomitant medication during the study;

8. History of relevant clinical allergic reactions of any origin;

9. Any other condition that in the opinion of the Investigator would interfere with the evaluation of the results or constitute a health risk for the subject;

10. Patients who are not willing to give informed consent (patient and/or parent/legal representative), or who withdraw consent.

11. Pregnant women in the 1st trimester of pregnancy.