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

NCT02605720 | Completed Phase 3 DMC

• 1 other identifier: LihirMC
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Malaria

Outcome Measures

Primary Outcomes (2)

• Change in QTcF interval (Fridericia's correction QT interval) after study drugs administration compared to baseline

  Day 58

• Plasma piperaquine concentrations after study drugs

  Day 58

Secondary Outcomes (2)

• Change in QTcF interval after study drugs administration compared to baseline

  Day 3

• Change in QTcF interval after study drugs administration compared to baseline

  Day 31

Study Arms (1)

Dihydroartemisinin-piperaquine

EXPERIMENTAL

Drug: Dihydroartemisinin-piperaquine

Interventions

Dihydroartemisinin-piperaquine DRUG

DHA/PPQ dose 2.1/17.1 mg/Kg daily for 3 days (PNG National Malaria Treatment Protocol) monthly for 3 months

Also known as: Eurartesim

Dihydroartemisinin-piperaquine

Eligibility Criteria

• Age: 3 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Male or female ≥3 years to ≤50 years
• Good general health by medical history physical examination, baseline electrocardiographs and laboratory tests.
• No clinically relevant abnormalities in blood pressure and heart rate
• 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.

You may not qualify if:

• A history of additional risk factors for Torsades-des-Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome);
• The use of concomitant medications that prolong the QT/QTc interval;
• 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;
• History of relevant clinical allergic reactions of any origin;
• 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;
• Patients who are not willing to give informed consent (patient and/or parent/legal representative), or who withdraw consent.
• Pregnant women in the 1st trimester of pregnancy.

Sponsors & Collaborators

• Lihir Medical Centre: lead
• Walter and Eliza Hall Institute of Medical Research: collaborator
• Papua New Guinea Institute of Medical Research: collaborator
• Barcelona Institute for Global Health: collaborator

Study Sites (1)

Lihir medical Centre

Londolovit, New Ireland Province, Papua New Guinea

Location

Related Publications (1)

• Millat-Martinez P, Salman S, Moore BR, Baro B, Page-Sharp M, Batty KT, Robinson LJ, Pomat W, Karunajeewa H, Laman M, Manning L, Mitja O, Bassat Q. Piperaquine Pharmacokinetic and Pharmacodynamic Profiles in Healthy Volunteers of Papua New Guinea after Administration of Three-Monthly Doses of Dihydroartemisinin-Piperaquine. Antimicrob Agents Chemother. 2022 Aug 16;66(8):e0018522. doi: 10.1128/aac.00185-22. Epub 2022 Jul 6.

  PMID: 35862743 DERIVED

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: November 12, 2015
• First Posted: November 16, 2015
• Study Start: September 1, 2015
• Primary Completion: January 1, 2016
• Study Completion: February 1, 2016
• Last Updated: March 3, 2016

Record last verified: 2016-02

Locations

PA (1)